10-110644623-G-C

Position:

• chr10-110644623-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134363.3(RBM20):​c.169G>C​(p.Gly57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 147,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19141021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.169G>C	p.Gly57Arg	missense_variant	1/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+1183G>C		intron_variant			XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.169G>C	p.Gly57Arg	missense_variant	1/14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes AF: 0.0000203 AC: 3 AN: 147542 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000756 AC: 9 AN: 1190654 Hom.: 0 Cov.: 35 AF XY: 0.00000678 AC XY: 4 AN XY: 590390

Gnomad4 AFR exome AF: 0.0000830

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000499

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000643

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000203 AC: 3 AN: 147678 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 72124

Gnomad4 AFR AF: 0.0000491

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.26	N
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.55	T
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.10	T
Vest4		0.11
MutPred		0.15		Gain of solvent accessibility (P = 0.0097);
MVP		0.47
ClinPred		0.89	D
GERP RS		0.54
gMVP		0.18

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: rs1395898788; hg19: chr10-112404381;