6-31765626-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025258.3(VWA7):​c.2644G>A​(p.Val882Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V882L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VWA7
NM_025258.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

0 publications found
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]
SAPCD1-AS1 (HGNC:39824): (SAPCD1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.08015385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VWA7NM_025258.3 linkc.2644G>A p.Val882Met missense_variant Exon 17 of 17 ENST00000375688.5 NP_079534.2 Q9Y334-1A0A1U9X8T7
SAPCD1-AS1NR_126423.1 linkn.-38G>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VWA7ENST00000375688.5 linkc.2644G>A p.Val882Met missense_variant Exon 17 of 17 5 NM_025258.3 ENSP00000364840.4 Q9Y334-1
SAPCD1-AS1ENST00000419679.1 linkn.-38G>A upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458932
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725662
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33436
American (AMR)
AF:
0.00
AC:
0
AN:
44444
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26070
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39684
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85948
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52162
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5556
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111378
Other (OTH)
AF:
0.00
AC:
0
AN:
60254
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
2.0
DANN
Benign
0.66
DEOGEN2
Benign
0.0062
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.028
N
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.0
L
PhyloP100
-0.89
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.030
N
REVEL
Benign
0.019
Sift
Benign
0.11
T
Sift4G
Benign
0.17
T
Polyphen
0.0020
B
Vest4
0.16
MutPred
0.28
Loss of catalytic residue at V882 (P = 0.0048);
MVP
0.061
MPC
0.31
ClinPred
0.034
T
GERP RS
-3.2
Varity_R
0.014
gMVP
0.24
Mutation Taster
=96/4
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

Publications

Other links and lift over

dbSNP: rs781076113; hg19: chr6-31733403; API