10-110644486-C-T

Variant summary

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

The NM_001134363.3(RBM20):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0240

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=0.22778681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM20	NM_001134363.3	c.32C>T	p.Ala11Val	missense_variant	1/14	ENST00000369519.4
RBM20	XM_017016103.3	c.26+1046C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.32C>T	p.Ala11Val	missense_variant	1/14	1	NM_001134363.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369322 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675418

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: 9.34e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 05, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.0024	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	19
Dann	Uncertain	1.0
Eigen	Benign	-0.086
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.62	D
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.35	T
MutationTaster	Benign	0.90	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.022	D
Vest4		0.084
MutPred		0.15		Gain of catalytic residue at A11 (P = 0.0087);
MVP		0.58
ClinPred		0.93	D
GERP RS		4.2
gMVP		0.22

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: rs794726895; hg19: chr10-112404244;