Variant rs727503391 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001134363.3(RBM20):c.3031G>A(p.Ala1011Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,399,440 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

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]

RBM20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.098027974).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RBM20	NM_001134363.3 linkuse as main transcript	c.3031G>A	p.Ala1011Thr	missense_variant	11/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3 linkuse as main transcript	c.2866G>A	p.Ala956Thr	missense_variant	11/14		XP_016871592.1
RBM20	XM_017016104.3 linkuse as main transcript	c.2647G>A	p.Ala883Thr	missense_variant	11/14		XP_016871593.1
RBM20	XM_047425116.1 linkuse as main transcript	c.2647G>A	p.Ala883Thr	missense_variant	11/14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4 linkuse as main transcript	c.3031G>A	p.Ala1011Thr	missense_variant	11/14	1	NM_001134363.3	ENSP00000358532	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1399440

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690220

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 27, 2013

The Ala1011Thr variant in RBM20 has not been reported in the literature or in la rge population studies. Alanine (Ala) at position 1011 is not conserved in mamma ls or evolutionarily distant species, and in fact, tree shrew has a Threonine (T hr) at this codon. Computational analyses (biochemical amino acid properties, co nservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully ass ess the clinical significance of the Ala1011Thr variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.072

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.47

MutationTaster

Benign

0.89

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.45

REVEL

Benign

0.21

Sift

Benign

0.19

Sift4G

Benign

0.29

Vest4

0.050

MutPred

0.12

Gain of phosphorylation at A1011 (P = 0.0051);

MVP

0.51

ClinPred

0.73

GERP RS

4.0

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over