1-201488917-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004078.3(CSRP1):​c.349G>A​(p.Glu117Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CSRP1
NM_004078.3 missense

Scores

2
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSRP1NM_004078.3 linkc.349G>A p.Glu117Lys missense_variant Exon 4 of 6 ENST00000340006.7 NP_004069.1 P21291A0A384P5K2
CSRP1NM_001193571.2 linkc.349G>A p.Glu117Lys missense_variant Exon 4 of 6 NP_001180500.1 P21291A0A384P5K2
CSRP1NM_001193572.2 linkc.349G>A p.Glu117Lys missense_variant Exon 4 of 6 NP_001180501.1 P21291A0A384P5K2
CSRP1NM_001193570.2 linkc.349G>A p.Glu117Lys missense_variant Exon 4 of 6 NP_001180499.1 P21291B4DY28

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSRP1ENST00000340006.7 linkc.349G>A p.Glu117Lys missense_variant Exon 4 of 6 1 NM_004078.3 ENSP00000345079.2 P21291

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251380
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461824
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.349G>A (p.E117K) alteration is located in exon 4 (coding exon 3) of the CSRP1 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the glutamic acid (E) at amino acid position 117 to be replaced by a lysine (K). 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
0.73
BayesDel_addAF
Uncertain
0.038
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;T;T;T;T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.98
.;D;D;.;.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.23
D
MutationAssessor
Uncertain
2.5
M;M;.;M;M;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.6
D;D;N;D;D;D;N
REVEL
Uncertain
0.45
Sift
Benign
0.097
T;T;D;T;T;T;D
Sift4G
Benign
0.13
T;T;T;T;T;T;.
Polyphen
0.67
P;P;.;P;P;.;.
Vest4
0.37
MutPred
0.49
Gain of MoRF binding (P = 0.0035);Gain of MoRF binding (P = 0.0035);Gain of MoRF binding (P = 0.0035);Gain of MoRF binding (P = 0.0035);Gain of MoRF binding (P = 0.0035);.;.;
MVP
0.92
MPC
0.28
ClinPred
0.89
D
GERP RS
5.5
Varity_R
0.42
gMVP
0.48

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: rs761072367; hg19: chr1-201458045; COSMIC: COSV100384676; COSMIC: COSV100384676; API