NM_173615.5:c.683C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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)
• Consequence: VWA3A NM_173615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

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

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=0.09609577).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173615.5. 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
	VWA3A	NM_173615.5	MANE Select	c.683C>G	p.Ala228Gly	missense	Exon 8 of 34	NP_775886.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA3A	ENST00000389398.10	TSL:5 MANE Select	c.683C>G	p.Ala228Gly	missense	Exon 8 of 34	ENSP00000374049.5	A6NCI4-1
	VWA3A	ENST00000568328.5	TSL:1	c.683C>G	p.Ala228Gly	missense	Exon 8 of 23	ENSP00000457770.1	H3BUS3
	VWA3A	ENST00000877573.1		c.683C>G	p.Ala228Gly	missense	Exon 8 of 33	ENSP00000547632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.11
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
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.044
Sift	Benign	0.33	T
Sift4G	Uncertain	0.027	D
Polyphen		0.37	B
Vest4		0.22
MutPred		0.35		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

Other links and lift over

hg19: chr16-22122309;