Variant rs397516853 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_003476.5(CSRP3):c.152C>T(p.Ala51Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CSRP3
NM_003476.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.85

Variant links:

Genes affected

CSRP3 (HGNC:2472): (cysteine and glycine rich protein 3) This gene encodes a member of the CSRP family 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 protein is found in a group of proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Mutations in this gene are thought to cause heritable forms of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in humans. Alternatively spliced transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

CSRP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a domain LIM zinc-binding 1 (size 51) in uniprot entity CSRP3_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_003476.5

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3239961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSRP3	NM_003476.5 link	c.152C>T	p.Ala51Val	missense_variant	3/6	ENST00000265968.9	NP_003467.1	P50461-1A2TDB8
CSRP3	NM_001369404.1 link	c.113-1917C>T		intron_variant			NP_001356333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSRP3	ENST00000265968.9 link	c.152C>T	p.Ala51Val	missense_variant	3/6	1	NM_003476.5	ENSP00000265968.3		P50461-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251060

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460612

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.31

T;.;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;D;.;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

-0.35

N;.;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.42

N;.;.;N

REVEL

Uncertain

0.43

Sift

Benign

0.31

T;.;.;T

Sift4G

Benign

0.33

T;.;.;T

Polyphen

0.0050

B;.;B;B

Vest4

0.70

MutPred

0.43

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.92

MPC

0.35

ClinPred

0.36

GERP RS

5.6

Varity_R

0.22

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over