10-110781748-G-C

Variant names:

• chr10-110781748-G-C
• rs777080028
• NM_001134363.3:c.1139G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001134363.3(RBM20):​c.1139G>C​(p.Arg380Pro) 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. 13/18 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. R380Q) 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: 2.77

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36367035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.1139G>C	p.Arg380Pro	missense_variant	Exon 2 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.974G>C	p.Arg325Pro	missense_variant	Exon 2 of 14		XP_016871592.1
RBM20	XM_017016104.3	c.755G>C	p.Arg252Pro	missense_variant	Exon 2 of 14		XP_016871593.1
RBM20	XM_047425116.1	c.755G>C	p.Arg252Pro	missense_variant	Exon 2 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.1139G>C	p.Arg380Pro	missense_variant	Exon 2 of 14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	0.037
Eigen_PC	Benign	0.017
FATHMM_MKL	Benign	0.57	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.32	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.17
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.070	T
Vest4		0.26
MutPred		0.34		Loss of MoRF binding (P = 0.0045);
MVP		0.44
ClinPred		0.74	D
GERP RS		3.4
gMVP		0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs777080028; hg19: chr10-112541506;