16-22110988-C-G

Variant names:

• chr16-22110988-C-G
• NM_173615.5:c.683C>G

Variant summary

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

The NM_173615.5(VWA3A):​c.683C>G​(p.Ala228Gly) 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. 15/21 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)
• Consequence: VWA3A NM_173615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

Genes affected

VWA3A (HGNC:27088): (von Willebrand factor A domain containing 3A) Predicted to be located in extracellular region. [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=0.09609577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA3A	NM_173615.5	c.683C>G	p.Ala228Gly	missense_variant	Exon 8 of 34	ENST00000389398.10	NP_775886.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA3A	ENST00000389398.10	c.683C>G	p.Ala228Gly	missense_variant	Exon 8 of 34	5	NM_173615.5	ENSP00000374049.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.683C>G (p.A228G) alteration is located in exon 8 (coding exon 8) of the VWA3A gene. This alteration results from a C to G substitution at nucleotide position 683, causing the alanine (A) at amino acid position 228 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.62
DEOGEN2	Benign	0.0031	.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	.;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.044
Sift	Benign	0.33	T;T
Sift4G	Uncertain	0.027	D;T
Polyphen		0.37	.;B
Vest4		0.22
MutPred		0.35		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);
MVP		0.040
MPC		0.062
ClinPred		0.27	T
GERP RS		0.74
Varity_R		0.069
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-22122309;