chr10-110644474-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate

The NM_001134363.3(RBM20):ā€‹c.20T>Gā€‹(p.Met7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,518,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M7L) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 7.3e-7 ( 0 hom. )

Consequence

RBM20
NM_001134363.3 missense

Scores

5
6
5

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.808
BP6
Variant 10-110644474-T-G is Benign according to our data. Variant chr10-110644474-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2030938.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RBM20NM_001134363.3 linkuse as main transcriptc.20T>G p.Met7Arg missense_variant 1/14 ENST00000369519.4
RBM20XM_017016103.3 linkuse as main transcriptc.26+1034T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RBM20ENST00000369519.4 linkuse as main transcriptc.20T>G p.Met7Arg missense_variant 1/141 NM_001134363.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152124
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000881
AC:
1
AN:
113462
Hom.:
0
AF XY:
0.0000159
AC XY:
1
AN XY:
62844
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 SAS exome
AF:
0.0000500
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.32e-7
AC:
1
AN:
1366524
Hom.:
0
Cov.:
31
AF XY:
0.00000148
AC XY:
1
AN XY:
674014
show subpopulations
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:
0.0000131
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152124
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 17, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
26
DANN
Uncertain
0.98
Eigen
Benign
0.13
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.79
D
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
-0.094
T
MutationTaster
Benign
0.78
D
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-0.41
N
REVEL
Uncertain
0.44
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.065
T
Vest4
0.84
MutPred
0.26
Gain of MoRF binding (P = 0.0662);
MVP
0.64
ClinPred
0.62
D
GERP RS
4.2
gMVP
0.53

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1027203249; hg19: chr10-112404232; API