19-35633109-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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. R181H) 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.541C>G	p.Arg181Gly	missense	Exon 6 of 10	NP_077297.2
	RBM42	NM_001319113.2		c.454C>G	p.Arg152Gly	missense	Exon 5 of 9	NP_001306042.1	Q9BTD8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM42	ENST00000262633.9	TSL:1 MANE Select	c.541C>G	p.Arg181Gly	missense	Exon 6 of 10	ENSP00000262633.3	Q9BTD8-1
	RBM42	ENST00000588161.5	TSL:1	c.451C>G	p.Arg151Gly	missense	Exon 5 of 9	ENSP00000466044.1	Q9BTD8-2
	RBM42	ENST00000943049.1		c.532C>G	p.Arg178Gly	missense	Exon 6 of 10	ENSP00000613108.1

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 v4.9

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
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.50	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
Polyphen		0.98	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;