3-47562647-C-T

Position:

• chr3-47562647-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006574.4(CSPG5):​c.1573G>A​(p.Asp525Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSPG5 NM_006574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30530757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPG5	NM_006574.4	c.1573G>A	p.Asp525Asn	missense_variant	5/5	ENST00000264723.9	NP_006565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPG5	ENST00000264723.9	c.1573G>A	p.Asp525Asn	missense_variant	5/5	1	NM_006574.4	ENSP00000264723.4
CSPG5	ENST00000383738.6	c.1654G>A	p.Asp552Asn	missense_variant	5/5	1		ENSP00000373244.2
CSPG5	ENST00000456150.5	c.1159G>A	p.Asp387Asn	missense_variant	4/4	1		ENSP00000392096.1
CSPG5	ENST00000610462.1	c.*63G>A		3_prime_UTR_variant	4/4	5		ENSP00000478923.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461792 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

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.: 31

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

May 01, 2024

The c.1654G>A (p.D552N) alteration is located in exon 5 (coding exon 5) of the CSPG5 gene. This alteration results from a G to A substitution at nucleotide position 1654, causing the aspartic acid (D) at amino acid position 552 to be replaced by an asparagine (N). 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	0.096
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	.;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	.;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.99, 0.99	.;D;D
Vest4		0.21
MutPred		0.47		.;Gain of methylation at K550 (P = 0.126);.;
MVP		0.37
MPC		1.5
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.17
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr3-47604137;