chr16-22097686-G-C

Variant names:

• chr16-22097686-G-C
• NM_173615.5:c.216G>C

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.216G>C​(p.Gln72His) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: VWA3A NM_173615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

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=0.07397947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA3A	NM_173615.5	c.216G>C	p.Gln72His	missense_variant	Exon 3 of 34	ENST00000389398.10	NP_775886.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA3A	ENST00000389398.10	c.216G>C	p.Gln72His	missense_variant	Exon 3 of 34	5	NM_173615.5	ENSP00000374049.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.216G>C (p.Q72H) alteration is located in exon 3 (coding exon 3) of the VWA3A gene. This alteration results from a G to C substitution at nucleotide position 216, causing the glutamine (Q) at amino acid position 72 to be replaced by a histidine (H). 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	0.29
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0029	.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M
PhyloP100		1.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.13
Sift	Benign	0.36	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.25	.;B
Vest4		0.49
MutPred		0.19		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.076
MPC		0.074
ClinPred		0.39	T
GERP RS		3.8
Varity_R		0.072
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-22109007;