rs77478951

Variant names:

• chr3-177038442-G-A
• rs77478951
• NM_024665.7:c.926-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-177038442-G-A
• chr3-177038442-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024665.7(TBL1XR1):​c.926-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 1,521,326 control chromosomes in the GnomAD database, including 7,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (597 hom., cov: 32)
  • Exomes 𝑓: 0.095 (6995 hom.)
• Consequence: TBL1XR1 NM_024665.7 splice_region, intron
• Scores: Splicing: ADA: 0.00002248
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.09
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-177038442-G-A is Benign according to our data. Variant chr3-177038442-G-A is described in ClinVar as [Benign]. Clinvar id is 448647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1XR1	NM_024665.7	c.926-8C>T		splice_region_variant, intron_variant	Intron 10 of 15	ENST00000457928.7	NP_078941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1XR1	ENST00000457928.7	c.926-8C>T		splice_region_variant, intron_variant	Intron 10 of 15	1	NM_024665.7	ENSP00000413251.3

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10708 AN: 152090 Hom.: 597 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0809

GnomAD2 exomes AF: 0.0710 AC: 10806 AN: 152134 AF XY: 0.0687

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.0524

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.000249

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0801

GnomAD4 exome AF: 0.0948 AC: 129776 AN: 1369118 Hom.: 6995 Cov.: 31 AF XY: 0.0922 AC XY: 62031 AN XY: 672956

African (AFR) AF: 0.0136 AC: 419 AN: 30894

American (AMR) AF: 0.0511 AC: 1549 AN: 30304

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 731 AN: 23070

East Asian (EAS) AF: 0.000134 AC: 5 AN: 37274

South Asian (SAS) AF: 0.0141 AC: 1019 AN: 72486

European-Finnish (FIN) AF: 0.113 AC: 5484 AN: 48714

Middle Eastern (MID) AF: 0.0148 AC: 81 AN: 5458

European-Non Finnish (NFE) AF: 0.109 AC: 116079 AN: 1064384

Other (OTH) AF: 0.0780 AC: 4409 AN: 56534

GnomAD4 genome AF: 0.0704 AC: 10709 AN: 152208 Hom.: 597 Cov.: 32 AF XY: 0.0699 AC XY: 5206 AN XY: 74430

African (AFR) AF: 0.0180 AC: 746 AN: 41542

American (AMR) AF: 0.0700 AC: 1072 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4828

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7261 AN: 67984

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0747 Hom.: 409

Bravo AF: 0.0654

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 26, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pierpont syndrome Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.83
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.020		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: rs77478951; hg19: chr3-176756230;