rs374414651

Variant names:

• chr3-177047407-A-G
• rs374414651
• NM_024665.7:c.767-10T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_024665.7(TBL1XR1):​c.767-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,592,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TBL1XR1 NM_024665.7 intron
• Scores: Splicing: ADA: 0.001354
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0700
• Publications: 0 publications found

Genes affected

TBL1XR1 (HGNC:29529): (TBL1X/Y related 1) This gene is a member of the WD40 repeat-containing gene family and shares sequence similarity with transducin (beta)-like 1X-linked (TBL1X). The protein encoded by this gene is thought to be a component of both nuclear receptor corepressor (N-CoR) and histone deacetylase 3 (HDAC 3) complexes, and is required for transcriptional activation by a variety of transcription factors. Mutations in these gene have been associated with some autism spectrum disorders, and one finding suggests that haploinsufficiency of this gene may be a cause of intellectual disability with dysmorphism. Mutations in this gene as well as recurrent translocations involving this gene have also been observed in some tumors. [provided by RefSeq, Mar 2016]

TBL1XR1-AS1 (HGNC:41243): (TBL1XR1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 3-177047407-A-G is Benign according to our data. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-177047407-A-G is described in CliVar as Likely_benign. Clinvar id is 536410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1XR1	NM_024665.7	c.767-10T>C		intron_variant	Intron 8 of 15	ENST00000457928.7	NP_078941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1XR1	ENST00000457928.7	c.767-10T>C		intron_variant	Intron 8 of 15	1	NM_024665.7	ENSP00000413251.3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000911 AC: 2 AN: 219616 AF XY: 0.00000839

Gnomad AFR exome AF: 0.000151

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000125 AC: 18 AN: 1440400 Hom.: 0 Cov.: 31 AF XY: 0.0000126 AC XY: 9 AN XY: 715106

African (AFR) AF: 0.000214 AC: 7 AN: 32648

American (AMR) AF: 0.00 AC: 0 AN: 42358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25602

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38752

South Asian (SAS) AF: 0.00 AC: 0 AN: 83576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100608

Other (OTH) AF: 0.000168 AC: 10 AN: 59354

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74482

African (AFR) AF: 0.000144 AC: 6 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000660 Hom.: 0

Bravo AF: 0.0000340

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pierpont syndrome Benign:1

Mar 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 02, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		-0.070
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.048
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374414651; hg19: chr3-176765195;