6-31766314-G-A

Variant names:

• chr6-31766314-G-A
• rs1333760995
• NM_025258.3:c.2255C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025258.3(VWA7):​c.2255C>T​(p.Ser752Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,478 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. S752W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VWA7 NM_025258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0864729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA7	NM_025258.3	c.2255C>T	p.Ser752Leu	missense_variant	Exon 15 of 17	ENST00000375688.5	NP_079534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5	c.2255C>T	p.Ser752Leu	missense_variant	Exon 15 of 17	5	NM_025258.3	ENSP00000364840.4
VWA7	ENST00000467576.1	n.2118C>T		non_coding_transcript_exon_variant	Exon 15 of 15	2
VWA7	ENST00000486423.5	n.763C>T		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459478 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725950

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111600

Other (OTH) AF: 0.0000166 AC: 1 AN: 60336

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.089
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.032
Sift	Benign	0.085	T
Sift4G	Benign	0.072	T
Polyphen		0.0070	B
Vest4		0.19
MutPred		0.64		Loss of disorder (P = 0.0133);
MVP		0.085
MPC		0.26
ClinPred		0.055	T
GERP RS		0.63
Varity_R		0.052
gMVP		0.51
Mutation Taster		=98/2	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: rs1333760995; hg19: chr6-31734091;