10-110821524-G-C

Position:

• chr10-110821524-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001134363.3(RBM20):​c.2905G>C​(p.Val969Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,672 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. 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. V969I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047601134).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.2905G>C	p.Val969Leu	missense_variant	11/14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.2740G>C	p.Val914Leu	missense_variant	11/14		XP_016871592.1
RBM20	XM_017016104.3	c.2521G>C	p.Val841Leu	missense_variant	11/14		XP_016871593.1
RBM20	XM_047425116.1	c.2521G>C	p.Val841Leu	missense_variant	11/14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.2905G>C	p.Val969Leu	missense_variant	11/14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000127 AC: 2 AN: 157576 Hom.: 0 AF XY: 0.0000240 AC XY: 2 AN XY: 83230

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: 0.00000500 AC: 7 AN: 1399672 Hom.: 0 Cov.: 33 AF XY: 0.0000101 AC XY: 7 AN XY: 690328

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: 0.0000883

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0020
DANN	Benign	0.48
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.073	N
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.70	T
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.23
Sift	Benign	0.59	T
Sift4G	Benign	0.74	T
Vest4		0.021
MutPred		0.19		Gain of loop (P = 0.1069);
MVP		0.088
ClinPred		0.023	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
gMVP		0.089

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: rs369747752; hg19: chr10-112581282;