rs878854248

chr10-110644588-C-CGCCGCCGCCCCA

Variant summary

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

The NM_001134363.3(RBM20):c.138_149dup(p.Gln49_Pro52dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,373,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P45P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RBM20 NM_001134363.3 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.123

Genes affected

RBM20 (HGNC:27424): (RNA binding motif protein 20) This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy. [provided by RefSeq, Apr 2014]

ACMG classification

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/exons	MANE	UniProt
RBM20	NM_001134363.3	c.138_149dup	p.Gln49_Pro52dup	inframe_insertion	1/14	ENST00000369519.4
RBM20	XM_017016103.3	c.26+1152_26+1163dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.138_149dup	p.Gln49_Pro52dup	inframe_insertion	1/14	1	NM_001134363.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1373680 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 677506

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000294

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: 9.33e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 1DD Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 16, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 238543). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.138_149dup, results in the insertion of 4 amino acid(s) of the RBM20 protein (p.Gln49_Pro52dup), but otherwise preserves the integrity of the reading frame. -

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: rs878854248; hg19: chr10-112404346;