6-31766614-G-T

Variant names:

• chr6-31766614-G-T
• rs547891848
• NM_025258.3:c.2033C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025258.3(VWA7):​c.2033C>A​(p.Pro678Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P678L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VWA7 NM_025258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052560538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA7	NM_025258.3	c.2033C>A	p.Pro678Gln	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.2033C>A	p.Pro678Gln	missense_variant	Exon 14 of 17	5	NM_025258.3	ENSP00000364840.4
VWA7	ENST00000467576.1	n.1896C>A		non_coding_transcript_exon_variant	Exon 14 of 15	2
VWA7	ENST00000486423.5	n.463C>A		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460716 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726680

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.099
DANN	Benign	0.80
DEOGEN2	Benign	0.00041	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.055	N
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.013
Sift	Benign	0.41	T
Sift4G	Benign	0.37	T
Polyphen		0.015	B
Vest4		0.14
MutPred		0.30		Gain of solvent accessibility (P = 0.0026);
MVP		0.072
MPC		0.28
ClinPred		0.036	T
GERP RS		-2.1
Varity_R		0.029
gMVP		0.27
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs547891848; hg19: chr6-31734391;