rs727503392

chr10-110821734-C-Gchr10-110821734-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.3115C>G(p.Pro1039Ala) 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 1,399,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1039S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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=0.08172089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM20	NM_001134363.3	c.3115C>G	p.Pro1039Ala	missense_variant	11/14	ENST00000369519.4
RBM20	XM_017016103.3	c.2950C>G	p.Pro984Ala	missense_variant	11/14
RBM20	XM_017016104.3	c.2731C>G	p.Pro911Ala	missense_variant	11/14
RBM20	XM_047425116.1	c.2731C>G	p.Pro911Ala	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.3115C>G	p.Pro1039Ala	missense_variant	11/14	1	NM_001134363.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000638 AC: 1 AN: 156848 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83072

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399456 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690232

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	16
Dann	Benign	0.91
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.64	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.22
Sift	Benign	0.23	T
Sift4G	Benign	0.50	T
Vest4		0.14
MutPred		0.13		Loss of loop (P = 0.0073);
MVP		0.32
ClinPred		0.075	T
GERP RS		5.0
gMVP		0.12

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: rs727503392; hg19: chr10-112581492;