rs281865416

Positions:

• chr11-19188253-TCCGA-CCCCT

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3 PP5

The NM_003476.5(CSRP3):​c.160_164delTCGGAinsAGGGG​(p.SerGlu54ArgGly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S54S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSRP3 NM_003476.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.93

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 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
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 11-19188253-TCCGA-CCCCT is Pathogenic according to our data. Variant chr11-19188253-TCCGA-CCCCT is described in ClinVar as [Pathogenic]. Clinvar id is 8779.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSRP3	NM_003476.5	c.160_164delTCGGAinsAGGGG	p.SerGlu54ArgGly	missense_variant		ENST00000265968.9	NP_003467.1
CSRP3	NM_001369404.1	c.113-1909_113-1905delTCGGAinsAGGGG		intron_variant			NP_001356333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSRP3	ENST00000265968.9	c.160_164delTCGGAinsAGGGG	p.SerGlu54ArgGly	missense_variant		1	NM_003476.5	ENSP00000265968.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypertrophic cardiomyopathy 12 Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 18, 2003	- -
not provided, no classification provided	literature only	ClinVar Staff, National Center for Biotechnology Information (NCBI)	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs281865416; hg19: chr11-19209800;