3-47569090-T-G

Variant names:

• chr3-47569090-T-G
• rs2031421892
• ENST00000383738.6:c.1520A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001206943.2(CSPG5):​c.1520A>C​(p.Tyr507Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y507C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CSPG5 NM_001206943.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206943.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPG5	NM_006574.4	MANE Select	c.1458+62A>C		intron	N/A	NP_006565.2	O95196-2
	CSPG5	NM_001206943.2		c.1520A>C	p.Tyr507Ser	missense	Exon 4 of 5	NP_001193872.1	O95196-1
	CSPG5	NM_001206945.2		c.1106A>C	p.Tyr369Ser	missense	Exon 4 of 5	NP_001193874.1	B7Z2E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPG5	ENST00000383738.6	TSL:1	c.1520A>C	p.Tyr507Ser	missense	Exon 4 of 5	ENSP00000373244.2	O95196-1
	CSPG5	ENST00000264723.9	TSL:1 MANE Select	c.1458+62A>C		intron	N/A	ENSP00000264723.4	O95196-2
	CSPG5	ENST00000456150.5	TSL:1	c.1044+62A>C		intron	N/A	ENSP00000392096.1	O95196-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398204 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691476

African (AFR) AF: 0.00 AC: 0 AN: 30564

American (AMR) AF: 0.00 AC: 0 AN: 32830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22208

East Asian (EAS) AF: 0.00 AC: 0 AN: 37664

South Asian (SAS) AF: 0.00 AC: 0 AN: 75342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5476

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1085138

Other (OTH) AF: 0.00 AC: 0 AN: 57784

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.027	D
Polyphen		0.55	P
Vest4		0.69
MutPred		0.69		Gain of disorder (P = 4e-04)
MVP		0.29
MPC		1.1
ClinPred		0.86	D
GERP RS		1.5
Varity_R		0.43
gMVP		0.30
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs2031421892; hg19: chr3-47610580;