RBM20 p.Phe443Leu

Variant names:

• chr10-110783419-C-A
• NM_001134363.3:c.1329C>A
• RBM20 p.Phe443Leu

Your query was ambiguous. Multiple possible variants found:

• chr10-110783419-C-A
• chr10-110783419-C-G
• chr10-110783417-T-C
• chr10-110783417-TTC-CTT
• chr10-110783417-TTC-CTA
• chr10-110783417-TTC-CTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134363.3(RBM20):​c.1329C>A​(p.Phe443Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25042057).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	NM_001134363.3	MANE Select	c.1329C>A	p.Phe443Leu	missense	Exon 3 of 14	NP_001127835.2	Q5T481

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.1329C>A	p.Phe443Leu	missense	Exon 3 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.1329C>A	p.Phe443Leu	missense	Exon 3 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.1329C>A	p.Phe443Leu	missense	Exon 3 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.43	T
PhyloP100		1.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.38
Sift	Benign	0.16	T
Sift4G	Benign	0.18	T
gMVP		0.64
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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.

Other links and lift over

hg19: chr10-112543177;