Genetic Variant RBM42:p.Val252Ala (chr19-35633757-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024321.5(RBM42):c.755T>C(p.Val252Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBM42
NM_024321.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.479

Publications

0 publications found

Variant links:

Genes affected

RBM42 (HGNC:28117): (RNA binding motif protein 42) Enables RNA binding activity. Predicted to act upstream of or within negative regulation of mRNA splicing, via spliceosome. Predicted to be located in cytoplasm and nucleus. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

RBM42 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15084267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM42	NM_024321.5 link	c.755T>C	p.Val252Ala	missense_variant	Exon 7 of 10	ENST00000262633.9	NP_077297.2	Q9BTD8-1
RBM42	NM_001319113.2 link	c.668T>C	p.Val223Ala	missense_variant	Exon 6 of 9		NP_001306042.1	Q9BTD8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM42	ENST00000262633.9 link	c.755T>C	p.Val252Ala	missense_variant	Exon 7 of 10	1	NM_024321.5	ENSP00000262633.3		Q9BTD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1344678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

661030

African (AFR)

AF:

0.00

AC:

AN:

27444

American (AMR)

AF:

0.00

AC:

AN:

26084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19428

East Asian (EAS)

AF:

0.00

AC:

AN:

34200

South Asian (SAS)

AF:

0.00

AC:

AN:

68158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061414

Other (OTH)

AF:

0.00

AC:

AN:

55206

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.755T>C (p.V252A) alteration is located in exon 7 (coding exon 7) of the RBM42 gene. This alteration results from a T to C substitution at nucleotide position 755, causing the valine (V) at amino acid position 252 to be replaced by an alanine (A). 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

0.059

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.054

.;T;T;T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.56

T;T;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.55

.;N;.;.;.

PhyloP100

0.48

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.57

.;N;.;.;.

REVEL

Benign

0.12

Sift

Benign

1.0

.;T;.;.;.

Sift4G

Benign

0.69

T;T;T;T;T

Polyphen

0.88

P;P;.;.;.

Vest4

0.32

MutPred

0.23

.;Gain of ubiquitination at K248 (P = 0.1051);.;.;.;

MVP

0.43

MPC

0.33

ClinPred

0.66

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.33

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over