3-47572696-G-T

Variant names:

• chr3-47572696-G-T
• rs776965190
• NM_006574.4:c.1372C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006574.4(CSPG5):​c.1372C>A​(p.Arg458Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSPG5 NM_006574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPG5	NM_006574.4	c.1372C>A	p.Arg458Ser	missense_variant	Exon 3 of 5	ENST00000264723.9	NP_006565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPG5	ENST00000264723.9	c.1372C>A	p.Arg458Ser	missense_variant	Exon 3 of 5	1	NM_006574.4	ENSP00000264723.4
CSPG5	ENST00000383738.6	c.1372C>A	p.Arg458Ser	missense_variant	Exon 3 of 5	1		ENSP00000373244.2
CSPG5	ENST00000456150.5	c.958C>A	p.Arg320Ser	missense_variant	Exon 2 of 4	1		ENSP00000392096.1
CSPG5	ENST00000610462.1	c.1372C>A	p.Arg458Ser	missense_variant	Exon 3 of 4	5		ENSP00000478923.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727124

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;T;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;L;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	N;N;N;.
REVEL	Benign	0.28
Sift	Uncertain	0.023	D;D;D;.
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.99, 0.98	.;D;D;.
Vest4		0.87
MutPred		0.82		.;Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);Loss of MoRF binding (P = 0.0159);
MVP		0.51
MPC		1.6
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.28
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs776965190; hg19: chr3-47614186;