chr11-124119051-G-C

Position:

• chr11-124119051-G-C

Variant summary

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

The NM_001130142.2(VWA5A):​c.722G>C​(p.Ser241Thr) 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: 33)
• Consequence: VWA5A NM_001130142.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

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=0.08856121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5A	NM_001130142.2	c.722G>C	p.Ser241Thr	missense_variant	7/19	ENST00000456829.7	NP_001123614.1
VWA5A	NM_014622.5	c.722G>C	p.Ser241Thr	missense_variant	6/18		NP_055437.2
VWA5A	NM_198315.3	c.722G>C	p.Ser241Thr	missense_variant	6/10		NP_938057.1
VWA5A	XM_011542828.3	c.770G>C	p.Ser257Thr	missense_variant	7/19		XP_011541130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5A	ENST00000456829.7	c.722G>C	p.Ser241Thr	missense_variant	7/19	1	NM_001130142.2	ENSP00000407726.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 13, 2023

The c.722G>C (p.S241T) alteration is located in exon 7 (coding exon 5) of the VWA5A gene. This alteration results from a G to C substitution at nucleotide position 722, causing the serine (S) at amino acid position 241 to be replaced by a threonine (T). 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	0.077
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.0027	T;.;.;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.51	.;.;T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.089	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L;L;.
MutationTaster	Benign	0.87	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.29	T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.010	B;.;.;B;B
Vest4		0.12
MutPred		0.36		Gain of glycosylation at S241 (P = 0.0426);Gain of glycosylation at S241 (P = 0.0426);Gain of glycosylation at S241 (P = 0.0426);Gain of glycosylation at S241 (P = 0.0426);.;
MVP		0.014
MPC		0.035
ClinPred		0.37	T
GERP RS		4.8
Varity_R		0.057
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr11-123989758;