11-124123790-G-A

Position:

• chr11-124123790-G-A

Variant summary

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

The NM_001130142.2(VWA5A):​c.1150G>A​(p.Gly384Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWA5A NM_001130142.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

VWA5A (HGNC:6658): (von Willebrand factor A domain containing 5A) Located in nucleoplasm. [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=0.186165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5A	NM_001130142.2	c.1150G>A	p.Gly384Ser	missense_variant	10/19	ENST00000456829.7	NP_001123614.1
VWA5A	NM_014622.5	c.1150G>A	p.Gly384Ser	missense_variant	9/18		NP_055437.2
VWA5A	NM_198315.3	c.1150G>A	p.Gly384Ser	missense_variant	9/10		NP_938057.1
VWA5A	XM_011542828.3	c.1198G>A	p.Gly400Ser	missense_variant	10/19		XP_011541130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5A	ENST00000456829.7	c.1150G>A	p.Gly384Ser	missense_variant	10/19	1	NM_001130142.2	ENSP00000407726	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.1150G>A (p.G384S) alteration is located in exon 10 (coding exon 8) of the VWA5A gene. This alteration results from a G to A substitution at nucleotide position 1150, causing the glycine (G) at amino acid position 384 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.90	.;.;D;D;D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M;M;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D;N;N;D;N
REVEL	Benign	0.079
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.78	P;.;.;P;P
Vest4		0.21
MutPred		0.49		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;
MVP		0.055
MPC		0.14
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.27

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: chr11-123994497;