3-177192806-G-T

Variant names:

• chr3-177192806-G-T
• rs11920602
• NM_024665.7:c.-122+4315C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024665.7(TBL1XR1):​c.-122+4315C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,196 control chromosomes in the GnomAD database, including 925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.064 (925 hom., cov: 33)
• Consequence: TBL1XR1 NM_024665.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 2 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 41

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• Pierpont syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024665.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1XR1	NM_024665.7	MANE Select	c.-122+4315C>A		intron	N/A	NP_078941.2
	TBL1XR1	NM_001321193.3		c.-122+3534C>A		intron	N/A	NP_001308122.1	Q9BZK7
	TBL1XR1	NM_001321194.3		c.-241+4315C>A		intron	N/A	NP_001308123.1	Q9BZK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1XR1	ENST00000457928.7	TSL:1 MANE Select	c.-122+4315C>A		intron	N/A	ENSP00000413251.3	Q9BZK7
	TBL1XR1	ENST00000430069.5	TSL:1	c.-122+3534C>A		intron	N/A	ENSP00000405574.1	Q9BZK7
	TBL1XR1	ENST00000352800.10	TSL:5	c.-46+4315C>A		intron	N/A	ENSP00000263964.11	Q9BZK7

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9714 AN: 152078 Hom.: 927 Cov.: 33

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00931

Gnomad OTH AF: 0.0564

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0639 AC: 9727 AN: 152196 Hom.: 925 Cov.: 33 AF XY: 0.0703 AC XY: 5231 AN XY: 74424

African (AFR) AF: 0.0911 AC: 3779 AN: 41498

American (AMR) AF: 0.105 AC: 1612 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2527 AN: 5172

South Asian (SAS) AF: 0.0507 AC: 245 AN: 4828

European-Finnish (FIN) AF: 0.0623 AC: 660 AN: 10596

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00931 AC: 633 AN: 68012

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0165 Hom.: 38

Bravo AF: 0.0717

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11920602; hg19: chr3-176910594;