rs942077

chr10-110835961-G-Achr10-110835961-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001134363.3(RBM20):c.3667G>A(p.Glu1223Lys) variant causes a missense change. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1223Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.12

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 10-110835961-G-A is Benign according to our data. Variant chr10-110835961-G-A is described in ClinVar as [Benign]. Clinvar id is 2765816.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM20	NM_001134363.3	c.3667G>A	p.Glu1223Lys	missense_variant	14/14	ENST00000369519.4
RBM20	XM_017016103.3	c.3502G>A	p.Glu1168Lys	missense_variant	14/14
RBM20	XM_017016104.3	c.3283G>A	p.Glu1095Lys	missense_variant	14/14
RBM20	XM_047425116.1	c.3283G>A	p.Glu1095Lys	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM20	ENST00000369519.4	c.3667G>A	p.Glu1223Lys	missense_variant	14/14	1	NM_001134363.3	P1
RBM20	ENST00000465774.2	n.608G>A		non_coding_transcript_exon_variant	2/2	4
RBM20	ENST00000480343.2	n.300G>A		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000218 AC: 3 AN: 137800 Hom.: 0 AF XY: 0.0000409 AC XY: 3 AN XY: 73424

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: 0.000146

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000451 AC: 5 AN: 1108846 Hom.: 0 Cov.: 14 AF XY: 0.00000718 AC XY: 4 AN XY: 557278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000438

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000564

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000452 AC: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 1DD Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.11
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.50	D
MutationTaster	Benign	0.0062	P
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.081	T
Vest4		0.20
MutPred		0.19		Gain of methylation at E1223 (P = 0.0016);
MVP		0.33
ClinPred		0.45	T
GERP RS		5.2
gMVP		0.33

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: rs942077; hg19: chr10-112595719;