Genetic Variant RBM38:p.Ala194Val (chr20-57407707-C-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.581C>T(p.Ala194Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,611,986 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 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

RBM38
NM_017495.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

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:

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=0.31325352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM38	NM_017495.6 link	c.581C>T	p.Ala194Val	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
RBM38	ENST00000356208.10 link	c.581C>T	p.Ala194Val	missense_variant	Exon 4 of 4	1	NM_017495.6	ENSP00000348538.5		Q9H0Z9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

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:

0.00000410

AC:

AN:

243634

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133462

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1459728

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74392

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.581C>T (p.A194V) 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 581, causing the alanine (A) at amino acid position 194 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.16

Sift

Benign

0.14

T;D

Sift4G

Benign

0.15

T;T

Polyphen

0.73

P;.

Vest4

0.51

MutPred

0.26

Loss of disorder (P = 0.065);.;

MVP

0.33

MPC

0.12

ClinPred

0.56

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.80

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