1-201490242-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004078.3(CSRP1):​c.215G>C​(p.Gly72Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

CSRP1
NM_004078.3 missense

Scores

14
3
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89
Variant links:
Genes affected
CSRP1 (HGNC:2469): (cysteine and glycine rich protein 1) This gene encodes a member of the cysteine-rich protein (CSRP) family. This gene family includes a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this gene product occurs in proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSRP1NM_004078.3 linkc.215G>C p.Gly72Ala missense_variant Exon 3 of 6 ENST00000340006.7 NP_004069.1 P21291A0A384P5K2
CSRP1NM_001193571.2 linkc.215G>C p.Gly72Ala missense_variant Exon 3 of 6 NP_001180500.1 P21291A0A384P5K2
CSRP1NM_001193572.2 linkc.215G>C p.Gly72Ala missense_variant Exon 3 of 6 NP_001180501.1 P21291A0A384P5K2
CSRP1NM_001193570.2 linkc.215G>C p.Gly72Ala missense_variant Exon 3 of 6 NP_001180499.1 P21291B4DY28

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSRP1ENST00000340006.7 linkc.215G>C p.Gly72Ala missense_variant Exon 3 of 6 1 NM_004078.3 ENSP00000345079.2 P21291

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000795
AC:
20
AN:
251432
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000855
AC:
125
AN:
1461872
Hom.:
0
Cov.:
30
AF XY:
0.0000784
AC XY:
57
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000869
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.215G>C (p.G72A) alteration is located in exon 3 (coding exon 2) of the CSRP1 gene. This alteration results from a G to C substitution at nucleotide position 215, causing the glycine (G) at amino acid position 72 to be replaced by an alanine (A). 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
0.98
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T;T;T;T;T;T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.99
.;D;D;.;.;D;D
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.81
D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Pathogenic
3.3
M;M;.;M;M;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-5.7
D;D;D;D;D;D;D
REVEL
Pathogenic
0.71
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;.
Polyphen
1.0
D;D;.;D;D;.;.
Vest4
0.75
MutPred
0.21
Loss of catalytic residue at P68 (P = 0.0741);Loss of catalytic residue at P68 (P = 0.0741);Loss of catalytic residue at P68 (P = 0.0741);Loss of catalytic residue at P68 (P = 0.0741);Loss of catalytic residue at P68 (P = 0.0741);.;.;
MVP
0.99
MPC
0.85
ClinPred
0.92
D
GERP RS
5.2
Varity_R
0.90
gMVP
0.49

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: rs770172252; hg19: chr1-201459370; COSMIC: COSV100384677; API