3-47577463-C-T

Position:

• chr3-47577463-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006574.4(CSPG5):​c.563G>A​(p.Gly188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G188V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSPG5 NM_006574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047734797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPG5	NM_006574.4	c.563G>A	p.Gly188Glu	missense_variant	2/5	ENST00000264723.9	NP_006565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPG5	ENST00000264723.9	c.563G>A	p.Gly188Glu	missense_variant	2/5	1	NM_006574.4	ENSP00000264723.4
CSPG5	ENST00000383738.6	c.563G>A	p.Gly188Glu	missense_variant	2/5	1		ENSP00000373244.2
CSPG5	ENST00000456150.5	c.149G>A	p.Gly50Glu	missense_variant	1/4	1		ENSP00000392096.1
CSPG5	ENST00000610462.1	c.563G>A	p.Gly188Glu	missense_variant	2/4	5		ENSP00000478923.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.089	.;T;.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	.;N;N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	1.1	N;N;N;.
REVEL	Benign	0.018
Sift	Benign	0.48	T;T;T;.
Sift4G	Benign	0.087	T;T;T;T
Polyphen		0.0070, 0.0010	.;B;B;.
Vest4		0.10
MutPred		0.35		.;Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);
MVP		0.14
MPC		0.73
ClinPred		0.068	T
GERP RS		0.84
Varity_R		0.074
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3732530; hg19: chr3-47618953;