rs993362892

Variant names:

• chr6-31766732-C-G
• rs993362892
• NM_025258.3:c.1915G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31766732-C-G
• chr6-31766732-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_025258.3(VWA7):​c.1915G>C​(p.Gly639Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: VWA7 NM_025258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA7	NM_025258.3	c.1915G>C	p.Gly639Arg	missense_variant	Exon 14 of 17	ENST00000375688.5	NP_079534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5	c.1915G>C	p.Gly639Arg	missense_variant	Exon 14 of 17	5	NM_025258.3	ENSP00000364840.4
VWA7	ENST00000467576.1	n.1778G>C		non_coding_transcript_exon_variant	Exon 14 of 15	2
VWA7	ENST00000486423.5	n.345G>C		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.74		Gain of solvent accessibility (P = 0.0128);
MVP		0.54
MPC		1.1
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.79
Mutation Taster		=82/18	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

Other links and lift over

dbSNP: rs993362892; hg19: chr6-31734509;