3-47577071-G-A

Variant summary

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

The NM_006574.4(CSPG5):​c.955C>T​(p.Arg319Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,490 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CSPG5
NM_006574.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34
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=0.17569137).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CSPG5NM_006574.4 linkuse as main transcriptc.955C>T p.Arg319Trp missense_variant 2/5 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.955C>T p.Arg319Trp missense_variant 2/51 NM_006574.4 ENSP00000264723.4 O95196-2
CSPG5ENST00000383738.6 linkuse as main transcriptc.955C>T p.Arg319Trp missense_variant 2/51 ENSP00000373244.2 O95196-1
CSPG5ENST00000456150.5 linkuse as main transcriptc.541C>T p.Arg181Trp missense_variant 1/41 ENSP00000392096.1 O95196-3
CSPG5ENST00000610462.1 linkuse as main transcriptc.955C>T p.Arg319Trp missense_variant 2/45 ENSP00000478923.1 A0A087WUT8

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152216
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1461274
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000331
Hom.:
0
Bravo
AF:
0.00000756

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 GeneticsSep 17, 2021The c.955C>T (p.R319W) alteration is located in exon 2 (coding exon 2) of the CSPG5 gene. This alteration results from a C to T substitution at nucleotide position 955, causing the arginine (R) at amino acid position 319 to be replaced by a tryptophan (W). 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
0.10
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;T;.;T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.38
N
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
.;N;N;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D;D;D;.
REVEL
Benign
0.13
Sift
Uncertain
0.0030
D;D;D;.
Sift4G
Uncertain
0.021
D;T;T;T
Polyphen
0.99, 1.0
.;D;D;.
Vest4
0.25
MutPred
0.36
.;Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP
0.51
MPC
1.4
ClinPred
0.71
D
GERP RS
4.2
Varity_R
0.16
gMVP
0.59

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: rs1268430299; hg19: chr3-47618561; API