NM_024321.5:c.541C>G

Variant names:

• chr19-35633109-C-G
• rs139455487
• NM_024321.5:c.541C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_024321.5(RBM42):​c.541C>G​(p.Arg181Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R181C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RBM42 NM_024321.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a modified_residue Asymmetric dimethylarginine (size 0) in uniprot entity RBM42_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM42	NM_024321.5	c.541C>G	p.Arg181Gly	missense_variant	Exon 6 of 10	ENST00000262633.9	NP_077297.2
RBM42	NM_001319113.2	c.454C>G	p.Arg152Gly	missense_variant	Exon 5 of 9		NP_001306042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM42	ENST00000262633.9	c.541C>G	p.Arg181Gly	missense_variant	Exon 6 of 10	1	NM_024321.5	ENSP00000262633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	.;T;T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T;D;T;T;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.50	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L;.;.;.
PhyloP100		3.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	.;N;.;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0050	.;D;.;.;.
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.98	D;D;.;.;.
Vest4		0.66
MutPred		0.37		.;Loss of methylation at R181 (P = 0.0131);.;.;.;
MVP		0.17
MPC		0.99
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.31
gMVP		0.35
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs139455487; hg19: chr19-36124011;