Variant chr11-124117845-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130142.2(VWA5A):c.216A>T(p.Lys72Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VWA5A
NM_001130142.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

VWA5A (HGNC:6658): (von Willebrand factor A domain containing 5A) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VWA5A links:

VWA5A (HGNC:):

VWA5A links:

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ACMG classification

Classification made for transcript

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=0.10228026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5A	NM_001130142.2 linkuse as main transcript	c.216A>T	p.Lys72Asn	missense_variant	4/19	ENST00000456829.7	NP_001123614.1	O00534-1A0A024R3H3
VWA5A	NM_014622.5 linkuse as main transcript	c.216A>T	p.Lys72Asn	missense_variant	3/18		NP_055437.2	O00534-1A0A024R3H3
VWA5A	NM_198315.3 linkuse as main transcript	c.216A>T	p.Lys72Asn	missense_variant	3/10		NP_938057.1	O00534-3
VWA5A	XM_011542828.3 linkuse as main transcript	c.264A>T	p.Lys88Asn	missense_variant	4/19		XP_011541130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5A	ENST00000456829.7 linkuse as main transcript	c.216A>T	p.Lys72Asn	missense_variant	4/19	1	NM_001130142.2	ENSP00000407726.2		O00534-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251490

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.216A>T (p.K72N) alteration is located in exon 4 (coding exon 2) of the VWA5A gene. This alteration results from a A to T substitution at nucleotide position 216, causing the lysine (K) at amino acid position 72 to be replaced by an asparagine (N). 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

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;.;.;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.63

.;.;T;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M;M;M;.

MutationTaster

Benign

0.67

D;D;D;D;D;D;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.4

N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.36

B;.;.;B;B

Vest4

0.16

MutPred

0.45

Loss of ubiquitination at K72 (P = 0.0412);Loss of ubiquitination at K72 (P = 0.0412);Loss of ubiquitination at K72 (P = 0.0412);Loss of ubiquitination at K72 (P = 0.0412);.;

MVP

0.014

MPC

0.050

ClinPred

0.090

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over