2-217809972-GAC-AAG

Variant names:

• chr2-217809972-GAC-AAG
• NM_001387777.1:c.5122_5124delGTCinsCTT
• TNS1 p.Val1708Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001387777.1(TNS1):​c.5122_5124delGTCinsCTT​(p.Val1708Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. V1708I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNS1 NM_001387777.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.23
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	NM_001387777.1	MANE Select	c.5122_5124delGTCinsCTT	p.Val1708Leu	missense	N/A	NP_001374706.1	Q9HBL0-3
	TNS1	NM_001438865.1		c.5185_5187delGTCinsCTT	p.Val1729Leu	missense	N/A	NP_001425794.1
	TNS1	NM_001438866.1		c.5119_5121delGTCinsCTT	p.Val1707Leu	missense	N/A	NP_001425795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	ENST00000682258.1	MANE Select	c.5122_5124delGTCinsCTT	p.Val1708Leu	missense	N/A	ENSP00000506917.1	Q9HBL0-3
	TNS1	ENST00000171887.8	TSL:1	c.4810_4812delGTCinsCTT	p.Val1604Leu	missense	N/A	ENSP00000171887.4	Q9HBL0-1
	TNS1	ENST00000419504.6	TSL:1	c.4768_4770delGTCinsCTT	p.Val1590Leu	missense	N/A	ENSP00000408724.1	E9PF55

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-218674695;