Variant 3-47572863-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006574.4(CSPG5):c.1205A>C(p.Gln402Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CSPG5
NM_006574.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.24

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPG5	NM_006574.4 linkuse as main transcript	c.1205A>C	p.Gln402Pro	missense_variant	3/5	ENST00000264723.9	NP_006565.2	O95196-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CSPG5	ENST00000264723.9 linkuse as main transcript	c.1205A>C	p.Gln402Pro	missense_variant	3/5	1	NM_006574.4	ENSP00000264723.4	O95196-2
CSPG5	ENST00000383738.6 linkuse as main transcript	c.1205A>C	p.Gln402Pro	missense_variant	3/5	1		ENSP00000373244.2	O95196-1
CSPG5	ENST00000456150.5 linkuse as main transcript	c.791A>C	p.Gln264Pro	missense_variant	2/4	1		ENSP00000392096.1	O95196-3
CSPG5	ENST00000610462.1 linkuse as main transcript	c.1205A>C	p.Gln402Pro	missense_variant	3/4	5		ENSP00000478923.1	A0A087WUT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723568

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Apr 07, 2022

The c.1205A>C (p.Q402P) alteration is located in exon 3 (coding exon 3) of the CSPG5 gene. This alteration results from a A to C substitution at nucleotide position 1205, causing the glutamine (Q) at amino acid position 402 to be replaced by a proline (P). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.75

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M;M;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.8

N;N;N;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.024

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.

Vest4

0.90

MutPred

0.38

.;Loss of catalytic residue at Q402 (P = 0.0528);Loss of catalytic residue at Q402 (P = 0.0528);Loss of catalytic residue at Q402 (P = 0.0528);

MVP

0.52

MPC

1.7

ClinPred

0.99

GERP RS

3.5

Varity_R

0.37

gMVP

0.99

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