GeneBe

13-41960891-T-C

Variant names:

Variant summary

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

The NM_015058.2(VWA8):​c.125A>G​(p.Glu42Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

VWA8
NM_015058.2 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Publications

0 publications found
Variant links:
Genes affected
VWA8 (HGNC:29071): (von Willebrand factor A domain containing 8) Predicted to enable ATP binding activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]
VWA8-AS1 (HGNC:44270): (VWA8 antisense RNA 1 (head to head))

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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=0.13012317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015058.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VWA8
NM_015058.2
MANE Select
c.125A>Gp.Glu42Gly
missense
Exon 1 of 45NP_055873.1A3KMH1-1
VWA8
NM_001009814.2
c.125A>Gp.Glu42Gly
missense
Exon 1 of 26NP_001009814.1A3KMH1-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VWA8
ENST00000379310.8
TSL:2 MANE Select
c.125A>Gp.Glu42Gly
missense
Exon 1 of 45ENSP00000368612.3A3KMH1-1
VWA8
ENST00000281496.6
TSL:1
c.125A>Gp.Glu42Gly
missense
Exon 1 of 26ENSP00000281496.6A3KMH1-2
VWA8
ENST00000938853.1
c.125A>Gp.Glu42Gly
missense
Exon 1 of 45ENSP00000608912.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1362140
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
672492
African (AFR)
AF:
0.00
AC:
0
AN:
28160
American (AMR)
AF:
0.00
AC:
0
AN:
34034
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24306
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32210
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78072
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34860
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4034
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1069644
Other (OTH)
AF:
0.00
AC:
0
AN:
56820
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.032
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PhyloP100
1.8
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.036
Sift
Uncertain
0.019
D
Sift4G
Benign
0.33
T
Polyphen
0.0
B
Vest4
0.11
MutPred
0.38
Gain of sheet (P = 4e-04)
MVP
0.088
MPC
0.067
ClinPred
0.22
T
GERP RS
3.7
PromoterAI
-0.13
Neutral
Varity_R
0.23
gMVP
0.44
Mutation Taster
=78/22
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1346244882; hg19: chr13-42535027; API