rs776965190

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-47572696-G-A
• chr3-47572696-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006574.4(CSPG5):​c.1372C>T​(p.Arg458Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000545 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R458H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: CSPG5 NM_006574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.22
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006574.4. 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.1372C>T	p.Arg458Cys	missense	Exon 3 of 5	NP_006565.2	O95196-2
	CSPG5	NM_001206943.2		c.1372C>T	p.Arg458Cys	missense	Exon 3 of 5	NP_001193872.1	O95196-1
	CSPG5	NM_001206944.2		c.1372C>T	p.Arg458Cys	missense	Exon 3 of 4	NP_001193873.1	A0A087WUT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPG5	ENST00000264723.9	TSL:1 MANE Select	c.1372C>T	p.Arg458Cys	missense	Exon 3 of 5	ENSP00000264723.4	O95196-2
	CSPG5	ENST00000383738.6	TSL:1	c.1372C>T	p.Arg458Cys	missense	Exon 3 of 5	ENSP00000373244.2	O95196-1
	CSPG5	ENST00000456150.5	TSL:1	c.958C>T	p.Arg320Cys	missense	Exon 2 of 4	ENSP00000392096.1	O95196-3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250546 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000540 AC: 79 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38 AN XY: 727124

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111862

Other (OTH) AF: 0.0000331 AC: 2 AN: 60384

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		6.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.83		Loss of disorder (P = 0.0064)
MVP		0.44
MPC		1.8
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.48
gMVP		0.86
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs776965190; hg19: chr3-47614186;