rs35042106

Variant names:

• chr5-83490420-C-G
• NM_004385.5:c.393C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-83490420-C-G
• chr5-83490420-C-T

Variant summary

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

The NM_004385.5(VCAN):​c.393C>G​(p.Asp131Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D131D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VCAN NM_004385.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

VCAN (HGNC:2464): (versican) This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

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=0.1067695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.393C>G	p.Asp131Glu	missense_variant	Exon 3 of 15	ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.393C>G	p.Asp131Glu	missense_variant	Exon 3 of 14		NP_001157569.1
VCAN	NM_001164098.2	c.393C>G	p.Asp131Glu	missense_variant	Exon 3 of 14		NP_001157570.1
VCAN	NM_001126336.3	c.393C>G	p.Asp131Glu	missense_variant	Exon 3 of 13		NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.393C>G	p.Asp131Glu	missense_variant	Exon 3 of 15	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.024
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T;.;.;T;.;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.85	D;D;D;T;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.11	T;T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-1.5	N;N;N;.;.;.;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.97	N;N;N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.20	T;T;T;T;T;T;T
Sift4G	Benign	0.84	T;T;T;T;D;T;T
Polyphen		0.87	P;P;D;.;.;B;B
Vest4		0.11
MutPred		0.54		Loss of phosphorylation at Y134 (P = 0.2173);Loss of phosphorylation at Y134 (P = 0.2173);Loss of phosphorylation at Y134 (P = 0.2173);.;Loss of phosphorylation at Y134 (P = 0.2173);Loss of phosphorylation at Y134 (P = 0.2173);Loss of phosphorylation at Y134 (P = 0.2173);
MVP		0.48
MPC		0.41
ClinPred		0.85	D
GERP RS		-9.1
Varity_R		0.095
gMVP		0.40

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.

Other links and lift over

hg19: chr5-82786239;