Genetic Variant NM_001387777.1:c.3901T>G (chr2-217818431-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387777.1(TNS1):c.3901T>G(p.Trp1301Gly) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W1301R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

TNS1
NM_001387777.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.70

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12519136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS1	NM_001387777.1 link	c.3901T>G	p.Trp1301Gly	missense_variant	Exon 24 of 33	ENST00000682258.1	NP_001374706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000682258.1 link	c.3901T>G	p.Trp1301Gly	missense_variant	Exon 24 of 33		NM_001387777.1	ENSP00000506917.1		Q9HBL0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.00075

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.040

.;T;.;T;T;T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.73

T;T;T;T;T;.;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.13

T;T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.0

.;N;.;.;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.87

.;N;.;.;.;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.016

.;D;.;.;.;D;D

Sift4G

Benign

0.32

.;T;T;T;T;T;T

Polyphen

0.0

.;B;.;B;.;B;B

Vest4

0.27, 0.14, 0.25, 0.25, 0.27, 0.29

MutPred

0.36

.;Gain of methylation at R1198 (P = 0.0252);.;.;.;.;.;

MVP

0.22

MPC

0.22

ClinPred

0.24

GERP RS

3.7

Varity_R

0.14

gMVP

0.41

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over