dbSNP rs759474596: CSPG5:p.Arg458Leu (chr3-47572695-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006574.4(CSPG5):c.1373G>T(p.Arg458Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CSPG5
NM_006574.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.55

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG5	NM_006574.4 link	c.1373G>T	p.Arg458Leu	missense_variant	Exon 3 of 5	ENST00000264723.9	NP_006565.2	O95196-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSPG5	ENST00000264723.9 link	c.1373G>T	p.Arg458Leu	missense_variant	Exon 3 of 5	1	NM_006574.4	ENSP00000264723.4	O95196-2
CSPG5	ENST00000383738.6 link	c.1373G>T	p.Arg458Leu	missense_variant	Exon 3 of 5	1		ENSP00000373244.2	O95196-1
CSPG5	ENST00000456150.5 link	c.959G>T	p.Arg320Leu	missense_variant	Exon 2 of 4	1		ENSP00000392096.1	O95196-3
CSPG5	ENST00000610462.1 link	c.1373G>T	p.Arg458Leu	missense_variant	Exon 3 of 4	5		ENSP00000478923.1	A0A087WUT8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250514

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135494

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727126

show subpopulations

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:

0.0000423

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

.;T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;L;L;.

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-4.1

D;D;D;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

D;D;D;.

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.93, 0.83

.;P;P;.

Vest4

0.62

MutPred

0.83

.;Loss of MoRF binding (P = 0.0143);Loss of MoRF binding (P = 0.0143);Loss of MoRF binding (P = 0.0143);

MVP

0.46

MPC

1.7

ClinPred

0.99

GERP RS

5.3

Varity_R

0.53

gMVP

0.87

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over