Genetic Variant CSRP3:c.-164_-162delAAA (chr11-19210493-CTTT-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The ENST00000533783.2(CSRP3):c.-164_-162delAAA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 98,982 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

CSRP3
ENST00000533783.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

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:

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

CSRP3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.125 (2/16) while in subpopulation NFE AF= 0.125 (2/16). AF 95% confidence interval is 0.0222. There are 0 homozygotes in gnomad4_exome. There are 1 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRP3-AS1	NR_183675.1 link	n.207+13591_207+13593delTTT		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRP3	ENST00000533783.2 link	c.-164_-162delAAA		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000431813.1		P50461-1
CSRP3-AS1	ENST00000527978.1 link	n.145+13591_145+13593delTTT		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.000121

AC:

AN:

98986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000224

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.125

GnomAD4 genome

AF:

0.000121

AC:

AN:

98966

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

46646

show subpopulations

Gnomad4 AFR

AF:

0.0000671

Gnomad4 AMR

AF:

0.000224

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00137

Gnomad4 NFE

AF:

0.0000445

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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