Genetic Variant RBM20:p.539 (chr10-110797592-CTG-TTA) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB4_Supporting

The NM_001134363.3(RBM20):c.1612_1614delCTGinsTTA (p.539) variant causes a synonymous change. The gene RBM20 is a known oncogene (CancerMine: 1 oncogene citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.86). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RBM20
NM_001134363.3 synonymous

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.86

Publications

0 publications found

Variant links:

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]

RBM20 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1DD
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: G2P
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RBM20 links:

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new If you want to explore the variant's impact on the transcript NM_001134363.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant outside canonical splice sites (B4 supporting); Synonymous variant — splicing impact not confirmed absent; B4 supporting [-1]

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001134363.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RBM20 NM_001134363.3	MANE Select	c.1612_1614delCTGinsTTA p.539	synonymous	N/A	Prot: NP_001127835.2 UniProt: Q5T481

RBM20 NM_001134363.3

MANE Select

HGVSc / HGVSpc.1612_1614delCTGinsTTAp.539

Exon rankN/A

synonymous

Prot: NP_001127835.2UniProt: Q5T481

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
RBM20 ENST00000369519.4	TSL:1MANE Select	c.1612_1614delCTGinsTTA p.539	synonymous	N/A	Prot: ENSP00000358532.3 UniProt: Q5T481
RBM20 ENST00000961386.1		c.1642_1644delCTGinsTTA p.549	synonymous	N/A	Prot: ENSP00000631445.1 UniProt: A0ACI8V4S1
RBM20 ENST00000718239.1		c.1612_1614delCTGinsTTA p.539	synonymous	N/A	Prot: ENSP00000520684.1 UniProt: Q5T481

RBM20 ENST00000369519.4

TSL:1MANE Select

HGVSc / HGVSpc.1612_1614delCTGinsTTAp.539

Exon rankN/A

synonymous

Prot: ENSP00000358532.3UniProt: Q5T481

RBM20 ENST00000961386.1

HGVSc / HGVSpc.1642_1644delCTGinsTTAp.549

Exon rankN/A

synonymous

Prot: ENSP00000631445.1UniProt: A0ACI8V4S1

RBM20 ENST00000718239.1

HGVSc / HGVSpc.1612_1614delCTGinsTTAp.539

Exon rankN/A

synonymous

Prot: ENSP00000520684.1UniProt: Q5T481

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	7.9

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence