Genetic Variant NM_001387777.1:c.321+2477C>A (chr2-217903858-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387777.1(TNS1):c.321+2477C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNS1
NM_001387777.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83

Publications

0 publications found

Variant links:

Genes affected

TNS1 (HGNC:11973): (tensin 1) The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

TNS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS1	NM_001387777.1 link	c.321+2477C>A		intron_variant	Intron 6 of 32	ENST00000682258.1	NP_001374706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000682258.1 link	c.321+2477C>A		intron_variant	Intron 6 of 32		NM_001387777.1	ENSP00000506917.1		Q9HBL0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

327598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

168656

African (AFR)

AF:

0.00

AC:

AN:

9294

American (AMR)

AF:

0.00

AC:

AN:

11342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11048

East Asian (EAS)

AF:

0.00

AC:

AN:

25272

South Asian (SAS)

AF:

0.00

AC:

AN:

17584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1636

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

206664

Other (OTH)

AF:

0.00

AC:

AN:

20610

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0060

(source)

DANN

Benign

0.47

PhyloP100

-2.8

PromoterAI

-0.079

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over