NM_001134363.3:c.850G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134363.3(RBM20):​c.850G>C​(p.Gly284Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000129 in 1,551,332 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G284E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

1
12
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.51

Publications

6 publications found
Variant links:
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]
RBM20 Gene-Disease associations (from GenCC):
  • dilated cardiomyopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • dilated cardiomyopathy 1DD
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM20NM_001134363.3 linkc.850G>C p.Gly284Arg missense_variant Exon 2 of 14 ENST00000369519.4 NP_001127835.2 Q5T481
RBM20XM_017016103.3 linkc.685G>C p.Gly229Arg missense_variant Exon 2 of 14 XP_016871592.1
RBM20XM_017016104.3 linkc.466G>C p.Gly156Arg missense_variant Exon 2 of 14 XP_016871593.1
RBM20XM_047425116.1 linkc.466G>C p.Gly156Arg missense_variant Exon 2 of 14 XP_047281072.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBM20ENST00000369519.4 linkc.850G>C p.Gly284Arg missense_variant Exon 2 of 14 1 NM_001134363.3 ENSP00000358532.3 Q5T481
RBM20ENST00000718239.1 linkc.850G>C p.Gly284Arg missense_variant Exon 2 of 14 ENSP00000520684.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000651
AC:
1
AN:
153600
AF XY:
0.0000123
show subpopulations
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000168
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399154
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
690090
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31598
American (AMR)
AF:
0.00
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25182
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49030
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
9.27e-7
AC:
1
AN:
1078970
Other (OTH)
AF:
0.00
AC:
0
AN:
57998
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41440
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
22
DANN
Pathogenic
1.0
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.51
D
MetaSVM
Uncertain
0.64
D
PhyloP100
6.5
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.43
Sift
Benign
0.14
T
Sift4G
Uncertain
0.0090
D
Vest4
0.55
MutPred
0.18
Loss of methylation at K280 (P = 0.073);
MVP
0.79
ClinPred
0.94
D
GERP RS
5.3
gMVP
0.61
Mutation Taster
=87/13
polymorphism

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

Other links and lift over

dbSNP: rs201148126; hg19: chr10-112541217; API