5-146229877-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_018989.2(RBM27):​c.556C>T​(p.Arg186Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R186H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RBM27
NM_018989.2 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41
Variant links:
Genes affected
RBM27 (HGNC:29243): (RNA binding motif protein 27) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be located in cytoplasm and nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3768106).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM27NM_018989.2 linkc.556C>T p.Arg186Cys missense_variant Exon 5 of 21 ENST00000265271.7 NP_061862.1 Q9P2N5
LOC127814297NM_001414499.1 linkc.556C>T p.Arg186Cys missense_variant Exon 5 of 20 NP_001401428.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBM27ENST00000265271.7 linkc.556C>T p.Arg186Cys missense_variant Exon 5 of 21 1 NM_018989.2 ENSP00000265271.5 Q9P2N5
ENSG00000275740ENST00000506502.2 linkc.556C>T p.Arg186Cys missense_variant Exon 5 of 20 5 ENSP00000475384.1 U3KPZ7

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151982
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.000479
GnomAD3 exomes
AF:
0.0000771
AC:
19
AN:
246396
Hom.:
0
AF XY:
0.0000820
AC XY:
11
AN XY:
134150
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000377
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000453
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461656
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
14
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
151982
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74210
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000197
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:
0.000479
Alfa
AF:
0.0000509
Hom.:
0
ExAC
AF:
0.0000664
AC:
8
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.556C>T (p.R186C) alteration is located in exon 5 (coding exon 5) of the RBM27 gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.31
.;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-4.6
.;D
REVEL
Benign
0.19
Sift
Uncertain
0.0010
.;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
.;D
Vest4
0.54
MVP
0.71
MPC
1.2
ClinPred
0.79
D
GERP RS
4.8
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.49
gMVP
0.36

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: rs202070436; hg19: chr5-145609440; COSMIC: COSV54590377; API