3-177192806-G-T

Position:

• chr3-177192806-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL1XR1	NM_024665.7	c.-122+4315C>A		intron_variant		ENST00000457928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1XR1	ENST00000457928.7	c.-122+4315C>A		intron_variant		1	NM_024665.7	P1

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

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.00931

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0164 Hom.: 32

Bravo AF: 0.0717

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs11920602; hg19: chr3-176910594;