3-47572696-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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 (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

CSPG5
NM_006574.4 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.856

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CSPG5NM_006574.4 linkuse as main transcriptc.1372C>T p.Arg458Cys missense_variant 3/5 ENST00000264723.9 NP_006565.2 O95196-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSPG5ENST00000264723.9 linkuse as main transcriptc.1372C>T p.Arg458Cys missense_variant 3/51 NM_006574.4 ENSP00000264723.4 O95196-2
CSPG5ENST00000383738.6 linkuse as main transcriptc.1372C>T p.Arg458Cys missense_variant 3/51 ENSP00000373244.2 O95196-1
CSPG5ENST00000456150.5 linkuse as main transcriptc.958C>T p.Arg320Cys missense_variant 2/41 ENSP00000392096.1 O95196-3
CSPG5ENST00000610462.1 linkuse as main transcriptc.1372C>T p.Arg458Cys missense_variant 3/45 ENSP00000478923.1 A0A087WUT8

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250546
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135504
show subpopulations
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 SAS exome
AF:
0.00
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
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

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2022The c.1372C>T (p.R458C) alteration is located in exon 3 (coding exon 3) of the CSPG5 gene. This alteration results from a C to T substitution at nucleotide position 1372, causing the arginine (R) at amino acid position 458 to be replaced by a cysteine (C). 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
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;.;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.057
D
MetaRNN
Pathogenic
0.86
D;D;D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.97
.;L;L;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-4.6
D;D;D;.
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;D;D;.
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
.;D;D;.
Vest4
0.83
MutPred
0.83
.;Loss of disorder (P = 0.0064);Loss of disorder (P = 0.0064);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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776965190; hg19: chr3-47614186; API