rs864622685

chr10-110812385-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001134363.3(RBM20):c.1988G>A(p.Gly663Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.46

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2616682).
• BP6: Variant 10-110812385-G-A is Benign according to our data. Variant chr10-110812385-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 220884.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM20	NM_001134363.3	c.1988G>A	p.Gly663Asp	missense_variant	9/14	ENST00000369519.4
RBM20	XM_017016103.3	c.1823G>A	p.Gly608Asp	missense_variant	9/14
RBM20	XM_017016104.3	c.1604G>A	p.Gly535Asp	missense_variant	9/14
RBM20	XM_047425116.1	c.1604G>A	p.Gly535Asp	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.1988G>A	p.Gly663Asp	missense_variant	9/14	1	NM_001134363.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000647 AC: 1 AN: 154584 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82272

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399346 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 1DD Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	0.11
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.030	D
Vest4		0.34
MutPred		0.15		Loss of catalytic residue at G663 (P = 0.0261);
MVP		0.54
ClinPred		0.70	D
GERP RS		1.6
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs864622685; hg19: chr10-112572143;