Genetic Variant NM_024321.5:c.839T>C (chr19-35633841-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.839T>C(p.Ile280Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,407,376 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: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RBM42
NM_024321.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

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=0.17714202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024321.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM42	NM_024321.5	MANE Select	c.839T>C	p.Ile280Thr	missense	Exon 7 of 10	NP_077297.2
	RBM42	NM_001319113.2		c.752T>C	p.Ile251Thr	missense	Exon 6 of 9	NP_001306042.1	Q9BTD8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM42	ENST00000262633.9	TSL:1 MANE Select	c.839T>C	p.Ile280Thr	missense	Exon 7 of 10	ENSP00000262633.3	Q9BTD8-1
RBM42	ENST00000588161.5	TSL:1	c.749T>C	p.Ile250Thr	missense	Exon 6 of 9	ENSP00000466044.1	Q9BTD8-2
RBM42	ENST00000943049.1		c.830T>C	p.Ile277Thr	missense	Exon 7 of 10	ENSP00000613108.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

176888

AF XY:

0.00

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:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1407376

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

698514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31808

American (AMR)

AF:

0.00

AC:

AN:

38828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24140

East Asian (EAS)

AF:

0.00

AC:

AN:

37356

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

1089106

Other (OTH)

AF:

0.0000171

AC:

AN:

58466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

Eigen

Benign

-0.021

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.0090

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

2.3

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.13

REVEL

Benign

0.083

Sift

Pathogenic

0.0

Sift4G

Benign

0.41

Polyphen

0.53

Vest4

0.60

MutPred

0.24

Gain of relative solvent accessibility (P = 0.0023)

MVP

0.16

MPC

0.35

ClinPred

0.37

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.59

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over