NM_001039500.3:c.539G>C

Variant names:

• chr1-20314568-G-C
• rs184297786
• NM_001039500.3:c.539G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039500.3(VWA5B1):​c.539G>C​(p.Gly180Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. G180D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: VWA5B1 NM_001039500.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456
• Publications: 0 publications found

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]

ENSG00000226664 (HGNC:41146):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06850526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA5B1	NM_001039500.3	c.539G>C	p.Gly180Ala	missense_variant	Exon 4 of 22	ENST00000289815.13	NP_001034589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA5B1	ENST00000289815.13	c.539G>C	p.Gly180Ala	missense_variant	Exon 4 of 22	5	NM_001039500.3	ENSP00000289815.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399338 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690178

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079000

Other (OTH) AF: 0.00 AC: 0 AN: 58046

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.9
DANN	Benign	0.85
DEOGEN2	Benign	0.0017	T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;L
PhyloP100		0.46
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.015
Sift	Benign	0.33	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.32	B;B
Vest4		0.093
MutPred		0.24		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.014
ClinPred		0.37	T
GERP RS		2.7
Varity_R		0.044
gMVP		0.30
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs184297786; hg19: chr1-20641061;