chr1-20336445-A-C

Position:

• chr1-20336445-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039500.3(VWA5B1):​c.1901A>C​(p.Lys634Thr) 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. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K634R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VWA5B1 NM_001039500.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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]

ACMG classification

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=0.07513434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5B1	NM_001039500.3	c.1901A>C	p.Lys634Thr	missense_variant	13/22	ENST00000289815.13	NP_001034589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5B1	ENST00000289815.13	c.1901A>C	p.Lys634Thr	missense_variant	13/22	5	NM_001039500.3	ENSP00000289815	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.1
DANN	Benign	0.78
DEOGEN2	Benign	0.0052	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.018
Sift	Benign	0.11	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.0070	B;B
Vest4		0.11
MutPred		0.41		Loss of ubiquitination at K634 (P = 0.0118);Loss of ubiquitination at K634 (P = 0.0118);
MVP		0.014
ClinPred		0.038	T
GERP RS		-2.1
Varity_R		0.085
gMVP		0.33

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

Other links and lift over

dbSNP: rs10916769; hg19: chr1-20662938;