NM_001387777.1:c.3901T>A

Variant names:

• chr2-217818431-A-T
• rs2571445
• NM_001387777.1:c.3901T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387777.1(TNS1):​c.3901T>A​(p.Trp1301Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029339314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS1	NM_001387777.1	c.3901T>A	p.Trp1301Arg	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>A	p.Trp1301Arg	missense_variant	Exon 24 of 33		NM_001387777.1	ENSP00000506917.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461692 Hom.: 0 Cov.: 91 AF XY: 0.00 AC XY: 0 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.67
DEOGEN2	Benign	0.033	.;T;.;T;T;T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.082	T;T;T;T;T;.;T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.029	T;T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-2.2	.;N;.;.;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	3.8	.;N;.;.;.;N;N
REVEL	Benign	0.15
Sift	Benign	1.0	.;T;.;.;.;T;T
Sift4G	Benign	0.52	.;T;T;T;T;T;T
Polyphen		0.0	.;B;.;B;.;B;B
Vest4		0.18, 0.080, 0.078, 0.16, 0.20, 0.20
MutPred		0.18		.;Gain of methylation at W1197 (P = 0.0296);.;.;.;.;.;
MVP		0.082
MPC		0.22
ClinPred		0.039	T
GERP RS		3.7
Varity_R		0.072
gMVP		0.33

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: rs2571445; hg19: chr2-218683154;