3-47569180-G-C

Position:

• chr3-47569180-G-C

Variant summary

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

The NM_006574.4(CSPG5):​c.1430C>G​(p.Ser477Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSPG5 NM_006574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85

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]

ACMG classification

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/exons	MANE	Protein	UniProt
CSPG5	NM_006574.4	c.1430C>G	p.Ser477Cys	missense_variant	4/5	ENST00000264723.9	NP_006565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPG5	ENST00000264723.9	c.1430C>G	p.Ser477Cys	missense_variant	4/5	1	NM_006574.4	ENSP00000264723.4
CSPG5	ENST00000383738.6	c.1430C>G	p.Ser477Cys	missense_variant	4/5	1		ENSP00000373244.2
CSPG5	ENST00000456150.5	c.1016C>G	p.Ser339Cys	missense_variant	3/4	1		ENSP00000392096.1
CSPG5	ENST00000610462.1	c.1382+3506C>G		intron_variant		5		ENSP00000478923.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2023

The c.1430C>G (p.S477C) alteration is located in exon 4 (coding exon 4) of the CSPG5 gene. This alteration results from a C to G substitution at nucleotide position 1430, causing the serine (S) at amino acid position 477 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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	.;D;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.97	.;L;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.6	D;D;N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.68
MutPred		0.74		.;Loss of disorder (P = 0.0263);Loss of disorder (P = 0.0263);
MVP		0.59
MPC		1.5
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-47610670;