rs1395898788

chr10-110644623-G-Achr10-110644623-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001134363.3(RBM20):c.169G>A(p.Gly57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000971 in 1,338,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G57D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03804949).
• BP6: Variant 10-110644623-G-A is Benign according to our data. Variant chr10-110644623-G-A is described in ClinVar as [Benign]. Clinvar id is 470588.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.169G>A	p.Gly57Ser	missense_variant	1/14	ENST00000369519.4
RBM20	XM_017016103.3	c.26+1183G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.169G>A	p.Gly57Ser	missense_variant	1/14	1	NM_001134363.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147544 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000216

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

GnomAD3 exomes AF: 0.0000284 AC: 3 AN: 105714 Hom.: 0 AF XY: 0.0000169 AC XY: 1 AN XY: 59096

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000459

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: 0.00000924 AC: 11 AN: 1190932 Hom.: 0 Cov.: 35 AF XY: 0.00000847 AC XY: 5 AN XY: 590518

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000111

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000857

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147544 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71990

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000216

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 1DD Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.95
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.27
Sift	Benign	0.61	T
Sift4G	Benign	0.53	T
Vest4		0.096
MutPred		0.070		Gain of glycosylation at G57 (P = 0.0173);
MVP		0.088
ClinPred		0.038	T
GERP RS		0.54
gMVP		0.14

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;