Variant 19-35633985-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000262633.9(RBM42):c.983G>A(p.Arg328Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,532,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

RBM42
ENST00000262633.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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:

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=0.09012097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM42	NM_024321.5 linkuse as main transcript	c.983G>A	p.Arg328Gln	missense_variant	7/10	ENST00000262633.9	NP_077297.2	Q9BTD8-1
RBM42	NM_001319113.2 linkuse as main transcript	c.896G>A	p.Arg299Gln	missense_variant	6/9		NP_001306042.1	Q9BTD8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM42	ENST00000262633.9 linkuse as main transcript	c.983G>A	p.Arg328Gln	missense_variant	7/10	1	NM_024321.5	ENSP00000262633.3		Q9BTD8-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

162846

Hom.:

AF XY:

0.00

AC XY:

AN XY:

89502

show subpopulations

Gnomad AFR exome

AF:

0.000169

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000724

AC:

AN:

1380276

Hom.:

Cov.:

AF XY:

0.00000735

AC XY:

AN XY:

680260

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000836

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.983G>A (p.R328Q) alteration is located in exon 7 (coding exon 7) of the RBM42 gene. This alteration results from a G to A substitution at nucleotide position 983, causing the arginine (R) at amino acid position 328 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

.;T;T;T;T

Eigen

Benign

-0.073

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

D;D;D;D;D

M_CAP

Benign

0.0061

MetaRNN

Benign

0.090

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

.;N;.;.;.

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.37

.;N;.;.;.

REVEL

Benign

0.11

Sift

Benign

0.038

.;D;.;.;.

Sift4G

Benign

0.65

T;T;T;T;T

Polyphen

0.52

P;B;.;.;.

Vest4

0.31

MutPred

0.19

.;Loss of methylation at R323 (P = 0.0687);.;.;.;

MVP

0.12

MPC

0.32

ClinPred

0.75

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.073

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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