Genetic Variant NM_024321.5:c.802G>A (chr19-35633804-G-A) – 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.802G>A(p.Val268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,499,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.000021 ( 0 hom. )

Consequence

RBM42
NM_024321.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Publications

1 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=0.22517765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM42	NM_024321.5 link	c.802G>A	p.Val268Met	missense_variant	Exon 7 of 10	ENST00000262633.9	NP_077297.2	Q9BTD8-1
RBM42	NM_001319113.2 link	c.715G>A	p.Val239Met	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.802G>A	p.Val268Met	missense_variant	Exon 7 of 10	1	NM_024321.5	ENSP00000262633.3		Q9BTD8-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

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

GnomAD2 exomes

AF:

0.0000185

AC:

AN:

107920

AF XY:

0.0000169

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000208

AC:

AN:

1347752

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

663884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28568

American (AMR)

AF:

0.00

AC:

AN:

26370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20176

East Asian (EAS)

AF:

0.0000287

AC:

AN:

34898

South Asian (SAS)

AF:

0.0000142

AC:

AN:

70258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5312

European-Non Finnish (NFE)

AF:

0.0000244

AC:

AN:

1065114

Other (OTH)

AF:

0.00

AC:

AN:

55762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000847

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.802G>A (p.V268M) 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 802, causing the valine (V) at amino acid position 268 to be replaced by a methionine (M). 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

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

.;T;T;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

.;N;.;.;.

PhyloP100

2.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.56

.;N;.;.;.

REVEL

Benign

0.096

Sift

Uncertain

0.0020

.;D;.;.;.

Sift4G

Benign

0.21

T;T;T;T;T

Polyphen

0.99

D;D;.;.;.

Vest4

0.47

MutPred

0.18

.;Loss of loop (P = 0.0374);.;.;.;

MVP

0.32

MPC

0.28

ClinPred

0.34

GERP RS

4.2

Varity_R

0.098

gMVP

0.36

Mutation Taster

=92/8

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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NM_024321.5:c.802G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over