NM_015058.2:c.125A>G

Variant names:

• chr13-41960891-T-C
• rs1346244882
• NM_015058.2:c.125A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

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))

ACMG classification

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA8	NM_015058.2	MANE Select	c.125A>G	p.Glu42Gly	missense	Exon 1 of 45	NP_055873.1	A3KMH1-1
	VWA8	NM_001009814.2		c.125A>G	p.Glu42Gly	missense	Exon 1 of 26	NP_001009814.1	A3KMH1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA8	ENST00000379310.8	TSL:2 MANE Select	c.125A>G	p.Glu42Gly	missense	Exon 1 of 45	ENSP00000368612.3	A3KMH1-1
	VWA8	ENST00000281496.6	TSL:1	c.125A>G	p.Glu42Gly	missense	Exon 1 of 26	ENSP00000281496.6	A3KMH1-2
	VWA8	ENST00000938853.1		c.125A>G	p.Glu42Gly	missense	Exon 1 of 45	ENSP00000608912.1

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

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

Other links and lift over

dbSNP: rs1346244882; hg19: chr13-42535027;