Variant 19-35633766-C-T 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.764C>T(p.Ala255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,494,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

RBM42
ENST00000262633.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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=0.09397301).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM42	NM_024321.5 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	7/10	ENST00000262633.9	NP_077297.2	Q9BTD8-1
RBM42	NM_001319113.2 linkuse as main transcript	c.677C>T	p.Ala226Val	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.764C>T	p.Ala255Val	missense_variant	7/10	1	NM_024321.5	ENSP00000262633.3		Q9BTD8-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000263

AC:

AN:

113906

Hom.:

AF XY:

0.000257

AC XY:

AN XY:

62348

show subpopulations

Gnomad AFR exome

AF:

0.000275

Gnomad AMR exome

AF:

0.000129

Gnomad ASJ exome

AF:

0.000428

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000843

Gnomad NFE exome

AF:

0.000430

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000482

AC:

647

AN:

1341998

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

302

AN XY:

659576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000387

Gnomad4 ASJ exome

AF:

0.0000515

Gnomad4 EAS exome

AF:

0.0000295

Gnomad4 SAS exome

AF:

0.0000146

Gnomad4 FIN exome

AF:

0.0000216

Gnomad4 NFE exome

AF:

0.000588

Gnomad4 OTH exome

AF:

0.000345

GnomAD4 genome

AF:

0.000243

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000206

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000586

AC:

ExAC

AF:

0.000109

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

Sep 27, 2021

The c.764C>T (p.A255V) alteration is located in exon 7 (coding exon 7) of the RBM42 gene. This alteration results from a C to T substitution at nucleotide position 764, causing the alanine (A) at amino acid position 255 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

.;T;T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.84

T;D;D;D;D

M_CAP

Benign

0.0090

MetaRNN

Benign

0.094

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N;.;.;.

MutationTaster

Benign

0.53

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

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.3

.;N;.;.;.

REVEL

Benign

0.090

Sift

Uncertain

0.014

.;D;.;.;.

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.88

P;P;.;.;.

Vest4

0.35

MVP

0.25

MPC

0.28

ClinPred

0.029

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.083

gMVP

0.41

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