Variant 6-31767376-C-A 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_025258.3(VWA7):c.1775G>T(p.Gly592Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,178 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VWA7
NM_025258.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0600

Variant links:

Genes affected

VWA7 (HGNC:13939): (von Willebrand factor A domain containing 7) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWA7 links:

Genome browser will be placed here

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=0.1336428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA7	NM_025258.3 linkuse as main transcript	c.1775G>T	p.Gly592Val	missense_variant	12/17	ENST00000375688.5	NP_079534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5 linkuse as main transcript	c.1775G>T	p.Gly592Val	missense_variant	12/17	5	NM_025258.3	ENSP00000364840	P1	Q9Y334-1
VWA7	ENST00000467576.1 linkuse as main transcript	n.1638G>T		non_coding_transcript_exon_variant	12/15	2
VWA7	ENST00000486423.5 linkuse as main transcript	n.205G>T		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461122

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726842

show subpopulations

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

AF:

0.0000132

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jun 17, 2022

The c.1775G>T (p.G592V) alteration is located in exon 12 (coding exon 11) of the VWA7 gene. This alteration results from a G to T substitution at nucleotide position 1775, causing the glycine (G) at amino acid position 592 to be replaced by a valine (V). 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

0.080

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.0081

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.60

REVEL

Benign

0.015

Sift

Benign

0.37

Sift4G

Benign

0.31

Polyphen

0.14

Vest4

0.26

MutPred

0.29

Gain of sheet (P = 0.0221);

MVP

0.067

MPC

0.39

ClinPred

0.055

GERP RS

2.8

Varity_R

0.036

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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