Genetic Variant CSPG5:p.Asn392Asp (chr3-47576852-T-C) – 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_006574.4(CSPG5):c.1174A>G(p.Asn392Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 1,566,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CSPG5
NM_006574.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

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=0.1450611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG5	NM_006574.4 link	c.1174A>G	p.Asn392Asp	missense_variant	Exon 2 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.1174A>G	p.Asn392Asp	missense_variant	Exon 2 of 5	1	NM_006574.4	ENSP00000264723.4	O95196-2
CSPG5	ENST00000383738.6 link	c.1174A>G	p.Asn392Asp	missense_variant	Exon 2 of 5	1		ENSP00000373244.2	O95196-1
CSPG5	ENST00000456150.5 link	c.760A>G	p.Asn254Asp	missense_variant	Exon 1 of 4	1		ENSP00000392096.1	O95196-3
CSPG5	ENST00000610462.1 link	c.1174A>G	p.Asn392Asp	missense_variant	Exon 2 of 4	5		ENSP00000478923.1	A0A087WUT8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

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:

0.00000462

AC:

AN:

216238

Hom.:

AF XY:

0.00000870

AC XY:

AN XY:

114976

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:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1414410

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697578

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:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

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

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1174A>G (p.N392D) alteration is located in exon 2 (coding exon 2) of the CSPG5 gene. This alteration results from a A to G substitution at nucleotide position 1174, causing the asparagine (N) at amino acid position 392 to be replaced by an aspartic acid (D). 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

0.27

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N;N;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

N;N;N;.

REVEL

Benign

0.092

Sift

Benign

0.36

T;T;T;.

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.97, 0.98

.;D;D;.

Vest4

0.32

MutPred

0.34

.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.27

MPC

1.4

ClinPred

0.75

GERP RS

4.6

Varity_R

0.26

gMVP

0.86

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