rs1554898774

Positions:

• chr10-110780926-CACAGACAGCT-CG

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_001134363.3(RBM20):​c.318_327delACAGACAGCTinsG​(p.Gln107_Ala109del) variant causes a conservative inframe deletion, synonymous 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 Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM20 NM_001134363.3 conservative_inframe_deletion, synonymous
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 8.91

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001134363.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.318_327delACAGACAGCTinsG	p.Gln107_Ala109del	conservative_inframe_deletion, synonymous_variant	2/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.153_162delACAGACAGCTinsG	p.Gln52_Ala54del	conservative_inframe_deletion, synonymous_variant	2/14		XP_016871592.1
RBM20	XM_017016104.3	c.-67_-58delACAGACAGCTinsG		5_prime_UTR_variant	2/14		XP_016871593.1
RBM20	XM_047425116.1	c.-67_-58delACAGACAGCTinsG		5_prime_UTR_variant	2/14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.318_327delACAGACAGCTinsG	p.Gln107_Ala109del	conservative_inframe_deletion, synonymous_variant	2/14	1	NM_001134363.3	ENSP00000358532.3

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: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dilated cardiomyopathy 1DD Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 28, 2023	The RBM20 c.318_327delinsG; p.Gln107_Ala109del variant (rs1554898774), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 538037). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant deletes three amino acid residues, leaving the rest of the protein in-frame. Due to limited information, the clinical significance of this variant is uncertain at this time. -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2023	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. This variant has not been reported in the literature in individuals affected with RBM20-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant, c.318_327delinsG, results in the deletion of 3 amino acid(s) of the RBM20 protein (p.Gln107_Ala109del), 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: rs1554898774; hg19: chr10-112540685;