Genetic Variant RBM38:p.Arg90Ser (chr20-57392686-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017495.6(RBM38):c.270G>T(p.Arg90Ser) 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 1,612,788 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. R90K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RBM38
NM_017495.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.206

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]

RBM38 links:

RBM38-AS1 (HGNC:40725): (RBM38 antisense RNA 1)

RBM38-AS1 links:

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;

BP4

Computational evidence support a benign effect (MetaRNN=0.35659096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM38	NM_017495.6 link	c.270G>T	p.Arg90Ser	missense_variant	Exon 2 of 4	ENST00000356208.10	NP_059965.2	Q9H0Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM38	ENST00000356208.10 link	c.270G>T	p.Arg90Ser	missense_variant	Exon 2 of 4	1	NM_017495.6	ENSP00000348538.5		Q9H0Z9-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

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:

0.000478

GnomAD3 exomes

AF:

0.0000445

AC:

AN:

247424

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460422

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.270G>T (p.R90S) alteration is located in exon 2 (coding exon 2) of the RBM38 gene. This alteration results from a G to T substitution at nucleotide position 270, causing the arginine (R) at amino acid position 90 to be replaced by a serine (S). 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

0.95

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

T;.;T

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.92

L;L;.

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0040

D;T;D

Polyphen

0.35

B;.;.

Vest4

0.87

MutPred

0.55

Gain of glycosylation at R90 (P = 0.0619);Gain of glycosylation at R90 (P = 0.0619);.;

MVP

0.81

MPC

2.4

ClinPred

0.47

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.89

gMVP

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over