10-110821789-G-T

Variant names:

• chr10-110821789-G-T
• rs188054898
• NM_001134363.3:c.3170G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134363.3(RBM20):​c.3170G>T​(p.Arg1057Leu) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1057G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05041969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.3170G>T	p.Arg1057Leu	missense_variant	Exon 11 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.3005G>T	p.Arg1002Leu	missense_variant	Exon 11 of 14		XP_016871592.1
RBM20	XM_017016104.3	c.2786G>T	p.Arg929Leu	missense_variant	Exon 11 of 14		XP_016871593.1
RBM20	XM_047425116.1	c.2786G>T	p.Arg929Leu	missense_variant	Exon 11 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.3170G>T	p.Arg1057Leu	missense_variant	Exon 11 of 14	1	NM_001134363.3	ENSP00000358532.3
RBM20	ENST00000718239.1	c.3170G>T	p.Arg1057Leu	missense_variant	Exon 11 of 14			ENSP00000520684.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.84
DANN	Uncertain	0.99
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.082	N
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.74	T
PhyloP100		-0.26
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.037	D
Sift4G	Benign	0.32	T
Vest4		0.091
ClinPred		0.11	T
GERP RS		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.11
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs188054898; hg19: chr10-112581547;