chr1-20312856-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001039500.3(VWA5B1):​c.160G>T​(p.Asp54Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

VWA5B1
NM_001039500.3 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VWA5B1NM_001039500.3 linkuse as main transcriptc.160G>T p.Asp54Tyr missense_variant 3/22 ENST00000289815.13 NP_001034589.2 Q5TIE3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VWA5B1ENST00000289815.13 linkuse as main transcriptc.160G>T p.Asp54Tyr missense_variant 3/225 NM_001039500.3 ENSP00000289815.9 Q5TIE3-2

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 29, 2024The c.160G>T (p.D54Y) alteration is located in exon 3 (coding exon 2) of the VWA5B1 gene. This alteration results from a G to T substitution at nucleotide position 160, causing the aspartic acid (D) at amino acid position 54 to be replaced by a tyrosine (Y). 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
0.30
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.062
T;.;.;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-5.3
D;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.012
D;D;D;D
Sift4G
Uncertain
0.011
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.64
MutPred
0.76
Gain of glycosylation at T57 (P = 0.1643);Gain of glycosylation at T57 (P = 0.1643);Gain of glycosylation at T57 (P = 0.1643);Gain of glycosylation at T57 (P = 0.1643);
MVP
0.19
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.52
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs937346243; hg19: chr1-20639349; API