3-47569106-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206943.2(CSPG5):​c.1504C>T​(p.Arg502Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 1,571,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CSPG5
NM_001206943.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12941867).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CSPG5NM_006574.4 linkuse as main transcriptc.1458+46C>T intron_variant ENST00000264723.9 NP_006565.2 O95196-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSPG5ENST00000383738.6 linkuse as main transcriptc.1504C>T p.Arg502Cys missense_variant 4/51 ENSP00000373244.2 O95196-1
CSPG5ENST00000264723.9 linkuse as main transcriptc.1458+46C>T intron_variant 1 NM_006574.4 ENSP00000264723.4 O95196-2
CSPG5ENST00000456150.5 linkuse as main transcriptc.1044+46C>T intron_variant 1 ENSP00000392096.1 O95196-3
CSPG5ENST00000610462.1 linkuse as main transcriptc.1382+3580C>T intron_variant 5 ENSP00000478923.1 A0A087WUT8

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
5
AN:
208902
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
113324
show subpopulations
Gnomad AFR exome
AF:
0.000140
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000130
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000510
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000162
AC:
23
AN:
1418884
Hom.:
0
Cov.:
31
AF XY:
0.0000128
AC XY:
9
AN XY:
704140
show subpopulations
Gnomad4 AFR exome
AF:
0.000161
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000105
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.00000914
Gnomad4 OTH exome
AF:
0.0000513
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567
ExAC
AF:
0.0000247
AC:
3

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 GeneticsAug 17, 2022The c.1504C>T (p.R502C) alteration is located in exon 4 (coding exon 4) of the CSPG5 gene. This alteration results from a C to T substitution at nucleotide position 1504, causing the arginine (R) at amino acid position 502 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
Benign
0.095
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
15
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.44
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.10
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.038
B
Vest4
0.17
MutPred
0.66
Loss of disorder (P = 0.046);
MVP
0.33
MPC
0.76
ClinPred
0.18
T
GERP RS
1.7
Varity_R
0.23
gMVP
0.31

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

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

Other links and lift over

dbSNP: rs527546433; hg19: chr3-47610596; API