20-57407674-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017495.6(RBM38):​c.548C>T​(p.Pro183Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,612,720 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

RBM38
NM_017495.6 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50
Variant links:
Genes affected
RBM38 (HGNC:15818): (RNA binding motif protein 38) Enables mRNA 3'-UTR binding activity. Involved in DNA damage response, signal transduction by p53 class mediator; negative regulation of cell population proliferation; and regulation of RNA metabolic process. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15970066).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM38NM_017495.6 linkc.548C>T p.Pro183Leu missense_variant Exon 4 of 4 ENST00000356208.10 NP_059965.2 Q9H0Z9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBM38ENST00000356208.10 linkc.548C>T p.Pro183Leu missense_variant Exon 4 of 4 1 NM_017495.6 ENSP00000348538.5 Q9H0Z9-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152138
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00000808
AC:
2
AN:
247438
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134716
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1460582
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
726638
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152138
Hom.:
0
Cov.:
34
AF XY:
0.0000135
AC XY:
1
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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:
0.0000491
ExAC
AF:
0.00000826
AC:
1
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
Jun 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.548C>T (p.P183L) alteration is located in exon 4 (coding exon 4) of the RBM38 gene. This alteration results from a C to T substitution at nucleotide position 548, causing the proline (P) at amino acid position 183 to be replaced by a leucine (L). 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
Benign
0.11
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.11
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.094
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.015
D;D
Polyphen
0.13
B;.
Vest4
0.33
MutPred
0.43
Gain of loop (P = 0.0013);.;
MVP
0.19
MPC
0.18
ClinPred
0.42
T
GERP RS
4.3
Varity_R
0.12
gMVP
0.65

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: rs747721670; hg19: chr20-55982730; API