Variant 1-1435803-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022834.5(VWA1):c.55C>T(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 1,032,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

VWA1
NM_022834.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814

Variant links:

Genes affected

VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

VWA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.395656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA1	NM_022834.5 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	1/3	ENST00000476993.2	NP_073745.2
VWA1	NM_199121.3 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	1/3		NP_954572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA1	ENST00000476993.2 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	1/3	1	NM_022834.5	ENSP00000417185	P1	Q6PCB0-1
VWA1	ENST00000471398.1 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	1/2	3		ENSP00000464343
VWA1	ENST00000338660.5 linkuse as main transcript	c.55C>T	p.Arg19Trp	missense_variant	1/3	2		ENSP00000423404		Q6PCB0-3
VWA1	ENST00000495558.1 linkuse as main transcript	c.-33+657C>T		intron_variant		2		ENSP00000463643

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000581

AC:

AN:

1032812

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

499920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000675

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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 16, 2022

The c.55C>T (p.R19W) alteration is located in exon 1 (coding exon 1) of the VWA1 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the arginine (R) at amino acid position 19 to be replaced by a tryptophan (W). 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

0.19

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;.

Eigen

Benign

0.017

Eigen_PC

Benign

-0.013

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.63

T;T;T

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.90

L;L;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-8.0

D;N;.

REVEL

Benign

0.23

Sift

Uncertain

0.0070

.;D;.

Sift4G

Uncertain

0.011

.;D;D

Polyphen

1.0

.;D;.

Vest4

0.34

MutPred

0.48

Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);

MVP

0.81

MPC

0.19

ClinPred

0.95

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.39

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