Variant 1-20312942-G-C 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_001039500.3(VWA5B1):c.246G>C(p.Glu82Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000786 in 1,399,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

VWA5B1
NM_001039500.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.491

Variant links:

Genes affected

VWA5B1 (HGNC:26538): (von Willebrand factor A domain containing 5B1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWA5B1 links:

(HGNC:):

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=0.07379478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5B1	NM_001039500.3 linkuse as main transcript	c.246G>C	p.Glu82Asp	missense_variant	3/22	ENST00000289815.13	NP_001034589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5B1	ENST00000289815.13 linkuse as main transcript	c.246G>C	p.Glu82Asp	missense_variant	3/22	5	NM_001039500.3	ENSP00000289815	A2	Q5TIE3-2
	ENST00000444923.1 linkuse as main transcript	n.85+10161C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000786

AC:

AN:

1399332

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690172

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.00

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:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000396

AC:

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

Jun 10, 2024

The c.246G>C (p.E82D) alteration is located in exon 3 (coding exon 2) of the VWA5B1 gene. This alteration results from a G to C substitution at nucleotide position 246, causing the glutamic acid (E) at amino acid position 82 to be replaced by an aspartic acid (D). 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

0.089

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0037

T;.;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.62

T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.041

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.67

N;N;.;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.090

N;N;N;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.021

.;B;.;.

Vest4

0.069

MutPred

0.28

Loss of ubiquitination at K78 (P = 0.1055);Loss of ubiquitination at K78 (P = 0.1055);Loss of ubiquitination at K78 (P = 0.1055);Loss of ubiquitination at K78 (P = 0.1055);

MVP

0.014

ClinPred

0.059

GERP RS

-1.3

Varity_R

0.037

gMVP

0.28

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