11-19210493-CT-C

Variant names:

• chr11-19210493-CT-C
• rs34865888
• ENST00000533783.2:c.-162delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000533783.2(CSRP3):​c.-162delA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.69 (22984 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSRP3 ENST00000533783.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.16

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-AS1 (HGNC:54183): (CSRP3 and E2F8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP3-AS1	NR_183675.1	n.207+13593delT		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP3	ENST00000533783.2	c.-162delA		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000431813.1
CSRP3-AS1	ENST00000527978.1	n.145+13593delT		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.686 AC: 67875 AN: 98948 Hom.: 22996 Cov.: 0

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.500 AC: 8 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.686 AC: 67848 AN: 98926 Hom.: 22984 Cov.: 0 AF XY: 0.686 AC XY: 32013 AN XY: 46634

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.705

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs34865888; hg19: chr11-19232040;