Genetic Variant VWA8:p.Gly9Arg (chr13-41960991-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015058.2(VWA8):c.25G>C(p.Gly9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,395,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

VWA8
NM_015058.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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 links:

VWA8-AS1 (HGNC:44270): (VWA8 antisense RNA 1 (head to head))

VWA8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01775825).

BP6

Variant 13-41960991-C-G is Benign according to our data. Variant chr13-41960991-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3189359.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 38 Unknown,AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VWA8	NM_015058.2	MANE Select	c.25G>C	p.Gly9Arg	missense	Exon 1 of 45	NP_055873.1	A3KMH1-1
VWA8	NM_001009814.2		c.25G>C	p.Gly9Arg	missense	Exon 1 of 26	NP_001009814.1	A3KMH1-2
VWA8-AS1	NR_039974.1		n.-178C>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VWA8	ENST00000379310.8	TSL:2 MANE Select	c.25G>C	p.Gly9Arg	missense	Exon 1 of 45	ENSP00000368612.3	A3KMH1-1
VWA8	ENST00000281496.6	TSL:1	c.25G>C	p.Gly9Arg	missense	Exon 1 of 26	ENSP00000281496.6	A3KMH1-2
VWA8	ENST00000938853.1		c.25G>C	p.Gly9Arg	missense	Exon 1 of 45	ENSP00000608912.1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000256

AC:

AN:

19516

AF XY:

0.000350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1243980

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

606276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24768

American (AMR)

AF:

0.00

AC:

AN:

14170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18258

East Asian (EAS)

AF:

0.00

AC:

AN:

27694

South Asian (SAS)

AF:

0.000447

AC:

AN:

58154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30424

Middle Eastern (MID)

AF:

0.000279

AC:

AN:

3582

European-Non Finnish (NFE)

AF:

0.00000788

AC:

AN:

1015642

Other (OTH)

AF:

0.0000585

AC:

AN:

51288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.0000264

AC:

AN:

151502

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41138

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.000624

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000651

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.017

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.68

M_CAP

Benign

0.082

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

PhyloP100

-1.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.050

REVEL

Benign

0.017

Sift

Benign

0.23

Sift4G

Benign

0.066

Polyphen

0.0070

Vest4

0.19

MutPred

0.26

Gain of MoRF binding (P = 0.0066)

MVP

0.014

MPC

0.064

ClinPred

0.067

GERP RS

-0.71

PromoterAI

0.015

Neutral

(source)

Varity_R

0.061

gMVP

0.42

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over