Variant 15-75676233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001897.5(CSPG4):c.6286C>T(p.Arg2096Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000282 in 1,553,490 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

CSPG4
NM_001897.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

CSPG4 (HGNC:2466): (chondroitin sulfate proteoglycan 4) A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [provided by RefSeq, Jul 2008]

CSPG4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3261904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPG4	NM_001897.5 linkuse as main transcript	c.6286C>T	p.Arg2096Cys	missense_variant	10/10	ENST00000308508.5
CSPG4	XM_047432196.1 linkuse as main transcript	c.5224C>T	p.Arg1742Cys	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPG4	ENST00000308508.5 linkuse as main transcript	c.6286C>T	p.Arg2096Cys	missense_variant	10/10	1	NM_001897.5	P1
	ENST00000569467.1 linkuse as main transcript	n.7G>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000812

AC:

AN:

160180

Hom.:

AF XY:

0.0000572

AC XY:

AN XY:

87478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000800

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000301

AC:

422

AN:

1401286

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

201

AN XY:

693646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000272

Gnomad4 ASJ exome

AF:

0.0000394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000735

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000372

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.000105

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.0000259

AC:

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 07, 2023

The c.6286C>T (p.R2096C) alteration is located in exon 10 (coding exon 10) of the CSPG4 gene. This alteration results from a C to T substitution at nucleotide position 6286, causing the arginine (R) at amino acid position 2096 to be replaced by a cysteine (C). 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

0.25

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.034

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.30

MutPred

0.45

Loss of MoRF binding (P = 0.0031);

MVP

0.43

MPC

1.2

ClinPred

0.86

GERP RS

4.6

Varity_R

0.27

gMVP

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over