rs1593717712

Variant names:

• chr13-41719673-T-C
• NM_015058.2:c.3034A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-41719673-T-C
• chr13-41719673-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015058.2(VWA8):​c.3034A>G​(p.Met1012Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. M1012L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VWA8 NM_015058.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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]

ACMG classification

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=0.09915793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA8	NM_015058.2	c.3034A>G	p.Met1012Val	missense_variant	Exon 26 of 45	ENST00000379310.8	NP_055873.1
VWA8	NM_001009814.2	c.3034A>G	p.Met1012Val	missense_variant	Exon 26 of 26		NP_001009814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA8	ENST00000379310.8	c.3034A>G	p.Met1012Val	missense_variant	Exon 26 of 45	2	NM_015058.2	ENSP00000368612.3
VWA8	ENST00000281496.6	c.3034A>G	p.Met1012Val	missense_variant	Exon 26 of 26	1		ENSP00000281496.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461050 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726838

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.095
Sift	Benign	0.64	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.040	B;.
Vest4		0.29
MutPred		0.62		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.030
MPC		0.057
ClinPred		0.14	T
GERP RS		-0.0061
Varity_R		0.097
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-42293809;