chr2-217818431-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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 Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TNS1 NM_001387777.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12519136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387777.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	NM_001387777.1	MANE Select	c.3901T>G	p.Trp1301Gly	missense	Exon 24 of 33	NP_001374706.1
	TNS1	NM_001438865.1		c.3964T>G	p.Trp1322Gly	missense	Exon 24 of 33	NP_001425794.1
	TNS1	NM_001438866.1		c.3901T>G	p.Trp1301Gly	missense	Exon 24 of 33	NP_001425795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	ENST00000682258.1	MANE Select	c.3901T>G	p.Trp1301Gly	missense	Exon 24 of 33	ENSP00000506917.1
	TNS1	ENST00000171887.8	TSL:1	c.3589T>G	p.Trp1197Gly	missense	Exon 24 of 33	ENSP00000171887.4
	TNS1	ENST00000419504.6	TSL:1	c.3550T>G	p.Trp1184Gly	missense	Exon 23 of 32	ENSP00000408724.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 91

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.12
Sift	Uncertain	0.016	D
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.27
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2571445; hg19: chr2-218683154;