Variant 1-1436939-C-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_022834.5(VWA1):c.86C>T(p.Ser29Leu) 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. 13/21 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VWA1
NM_022834.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.123

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:

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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=0.16898242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA1	NM_022834.5 linkuse as main transcript	c.86C>T	p.Ser29Leu	missense_variant	2/3	ENST00000476993.2	NP_073745.2
VWA1	NM_199121.3 linkuse as main transcript	c.74-383C>T		intron_variant			NP_954572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA1	ENST00000476993.2 linkuse as main transcript	c.86C>T	p.Ser29Leu	missense_variant	2/3	1	NM_022834.5	ENSP00000417185	P1	Q6PCB0-1
VWA1	ENST00000471398.1 linkuse as main transcript	c.206C>T	p.Ser69Leu	missense_variant	2/2	3		ENSP00000464343
VWA1	ENST00000495558.1 linkuse as main transcript	c.-20C>T		5_prime_UTR_variant	2/2	2		ENSP00000463643
VWA1	ENST00000338660.5 linkuse as main transcript	c.74-383C>T		intron_variant		2		ENSP00000423404		Q6PCB0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1443402

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715686

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:

0.00

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

Dec 11, 2023

The c.86C>T (p.S29L) alteration is located in exon 2 (coding exon 2) of the VWA1 gene. This alteration results from a C to T substitution at nucleotide position 86, causing the serine (S) at amino acid position 29 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.037

Sift

Uncertain

0.0050

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.48

P;.

Vest4

0.20

MutPred

0.32

Loss of phosphorylation at S29 (P = 0.0107);.;

MVP

0.55

MPC

0.032

ClinPred

0.40

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over