10-110823507-C-A

Position:

• chr10-110823507-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001134363.3(RBM20):​c.3344C>A​(p.Ser1115Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000149 in 1,343,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43

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 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity RBM20_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23007289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.3344C>A	p.Ser1115Tyr	missense_variant	12/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.3179C>A	p.Ser1060Tyr	missense_variant	12/14		XP_016871592.1
RBM20	XM_017016104.3	c.2960C>A	p.Ser987Tyr	missense_variant	12/14		XP_016871593.1
RBM20	XM_047425116.1	c.2960C>A	p.Ser987Tyr	missense_variant	12/14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.3344C>A	p.Ser1115Tyr	missense_variant	12/14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.0000130 AC: 2 AN: 153270 Hom.: 0 AF XY: 0.0000123 AC XY: 1 AN XY: 81162

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: 0.0000597

Gnomad NFE exome AF: 0.0000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1343450 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 661488

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: 0.0000222

Gnomad4 NFE exome AF: 9.58e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ExAC AF: 0.0000421 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.00081	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.070	T
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Vest4		0.26
MutPred		0.35		Gain of sheet (P = 0.0125);
MVP		0.76
ClinPred		0.80	D
GERP RS		6.2
gMVP		0.39

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: rs769531546; hg19: chr10-112583265; COSMIC: COSV101051428; COSMIC: COSV101051428;