2-217818431-A-C

Variant names:

• chr2-217818431-A-C
• NM_001387777.1:c.3901T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70

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]

ACMG classification

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	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	c.3901T>G	p.Trp1301Gly	missense_variant	Exon 24 of 33		NM_001387777.1	ENSP00000506917.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 91

GnomAD4 genome Cov.: 34

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	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
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	D
LIST_S2	Benign	0.73	T;T;T;T;T;.;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.;.
PrimateAI	Uncertain	0.50	T
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	T
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.

Other links and lift over

hg19: chr2-218683154;