Genetic Variant CSPG5:p.Arg502Cys (chr3-47569106-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206943.2(CSPG5):c.1504C>T(p.Arg502Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 1,571,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CSPG5
NM_001206943.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

CSPG5 (HGNC:2467): (chondroitin sulfate proteoglycan 5) The protein encoded by this gene is a proteoglycan that may function as a neural growth and differentiation factor. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

CSPG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12941867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG5	NM_006574.4 link	c.1458+46C>T		intron_variant	Intron 4 of 4	ENST00000264723.9	NP_006565.2	O95196-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSPG5	ENST00000383738.6 link	c.1504C>T	p.Arg502Cys	missense_variant	Exon 4 of 5	1		ENSP00000373244.2	O95196-1
CSPG5	ENST00000264723.9 link	c.1458+46C>T		intron_variant	Intron 4 of 4	1	NM_006574.4	ENSP00000264723.4	O95196-2
CSPG5	ENST00000456150.5 link	c.1044+46C>T		intron_variant	Intron 3 of 3	1		ENSP00000392096.1	O95196-3
CSPG5	ENST00000610462.1 link	c.1382+3580C>T		intron_variant	Intron 3 of 3	5		ENSP00000478923.1	A0A087WUT8

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

208902

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113324

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000130

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000510

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

1418884

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

704140

show subpopulations

Gnomad4 AFR exome

AF:

0.000161

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000105

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.00000914

Gnomad4 OTH exome

AF:

0.0000513

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1504C>T (p.R502C) alteration is located in exon 4 (coding exon 4) of the CSPG5 gene. This alteration results from a C to T substitution at nucleotide position 1504, causing the arginine (R) at amino acid position 502 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

0.095

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Benign

0.018

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.10

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.038

Vest4

0.17

MutPred

0.66

Loss of disorder (P = 0.046);

MVP

0.33

MPC

0.76

ClinPred

0.18

GERP RS

1.7

Varity_R

0.23

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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