Variant chr14-76762825-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014909.5(VASH1):c.4C>T(p.Pro2Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000015 in 1,336,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

VASH1
NM_014909.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22

Variant links:

Genes affected

VASH1 (HGNC:19964): (vasohibin 1) Enables actin binding activity and metallocarboxypeptidase activity. Involved in negative regulation of angiogenesis; negative regulation of blood vessel endothelial cell migration; and proteolysis. Acts upstream of or within several processes, including negative regulation of endothelial cell migration; negative regulation of endothelial cell proliferation; and negative regulation of lymphangiogenesis. Located in apical part of cell; endoplasmic reticulum; and extracellular space. Implicated in liver cirrhosis and portal hypertension. Biomarker of liver cirrhosis. [provided by Alliance of Genome Resources, Apr 2022]

VASH1 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=0.20015135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VASH1	NM_014909.5 linkuse as main transcript	c.4C>T	p.Pro2Ser	missense_variant	1/7	ENST00000167106.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VASH1	ENST00000167106.9 linkuse as main transcript	c.4C>T	p.Pro2Ser	missense_variant	1/7	1	NM_014909.5	P1	Q7L8A9-1
VASH1	ENST00000554237.1 linkuse as main transcript	c.4C>T	p.Pro2Ser	missense_variant	1/4	1			Q7L8A9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1336276

Hom.:

Cov.:

AF XY:

0.00000307

AC XY:

AN XY:

651728

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000381

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:

9.51e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.4C>T (p.P2S) alteration is located in exon 1 (coding exon 1) of the VASH1 gene. This alteration results from a C to T substitution at nucleotide position 4, causing the proline (P) at amino acid position 2 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.60

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.033

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.050

T;D

Polyphen

0.0010

B;B

Vest4

0.39

MutPred

0.26

Gain of phosphorylation at P2 (P = 0.0079);Gain of phosphorylation at P2 (P = 0.0079);

MVP

0.043

MPC

0.56

ClinPred

0.60

GERP RS

4.1

Varity_R

0.16

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over