rs2462634

Variant names:

• chr7-47394031-T-C
• rs2462634
• NM_022748.12:c.1024+2769A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022748.12(TNS3):​c.1024+2769A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,878 control chromosomes in the GnomAD database, including 34,855 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 0.68 (34855 hom., cov: 30)
• Consequence: TNS3 NM_022748.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

Genes affected

TNS3 (HGNC:21616): (tensin 3) Predicted to enable phosphatase activity. Predicted to be involved in dephosphorylation and intracellular signal transduction. Predicted to act upstream of or within cell migration; lung alveolus development; and positive regulation of cell population proliferation. Located in cytosol and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS3	NM_022748.12	c.1024+2769A>G		intron_variant	Intron 16 of 30	ENST00000311160.14	NP_073585.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS3	ENST00000311160.14	c.1024+2769A>G		intron_variant	Intron 16 of 30	1	NM_022748.12	ENSP00000312143.9

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102527 AN: 151760 Hom.: 34816 Cov.: 30

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.676 AC: 102628 AN: 151878 Hom.: 34855 Cov.: 30 AF XY: 0.676 AC XY: 50215 AN XY: 74258

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.683

Alfa AF: 0.674 Hom.: 5409

Bravo AF: 0.673

Asia WGS AF: 0.688 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.59

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: rs2462634; hg19: chr7-47433628;