rs878854253

Positions:

• chr10-110780961-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000369519.4(RBM20):​c.352A>G​(p.Thr118Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,399,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T118I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: RBM20 ENST00000369519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12

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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.352A>G	p.Thr118Ala	missense_variant	2/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.187A>G	p.Thr63Ala	missense_variant	2/14		XP_016871592.1
RBM20	XM_017016104.3	c.-33A>G		5_prime_UTR_variant	2/14		XP_016871593.1
RBM20	XM_047425116.1	c.-33A>G		5_prime_UTR_variant	2/14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.352A>G	p.Thr118Ala	missense_variant	2/14	1	NM_001134363.3	ENSP00000358532	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000128 AC: 2 AN: 156618 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 82988

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000878

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399444 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000631

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 1DD Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.71	D
MutationTaster	Benign	0.93	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.084	T
Vest4		0.52
MutPred		0.33		Loss of glycosylation at T118 (P = 0.0248);
MVP		0.89
ClinPred		0.88	D
GERP RS		4.7
gMVP		0.43

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: rs878854253; hg19: chr10-112540719;