NM_024321.5:c.49G>C

Variant names:

• chr19-35629202-G-C
• NM_024321.5:c.49G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024321.5(RBM42):​c.49G>C​(p.Val17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM42 NM_024321.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.207
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10013422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM42	NM_024321.5	c.49G>C	p.Val17Leu	missense_variant	Exon 1 of 10	ENST00000262633.9	NP_077297.2
RBM42	NM_001319113.2	c.49G>C	p.Val17Leu	missense_variant	Exon 1 of 9		NP_001306042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM42	ENST00000262633.9	c.49G>C	p.Val17Leu	missense_variant	Exon 1 of 10	1	NM_024321.5	ENSP00000262633.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.49G>C (p.V17L) alteration is located in exon 1 (coding exon 1) of the RBM42 gene. This alteration results from a G to C substitution at nucleotide position 49, causing the valine (V) at amino acid position 17 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	.;T;T;.;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.062	N
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.;.;.;.
PhyloP100		0.21
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.24	.;N;.;.;.;.
REVEL	Benign	0.037
Sift	Pathogenic	0.0	.;D;.;.;.;.
Sift4G	Benign	0.092	T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.14
MutPred		0.23		Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);Gain of relative solvent accessibility (P = 0.2363);
MVP		0.068
MPC		1.0
ClinPred		0.49	T
GERP RS		2.6
PromoterAI		0.066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.095
gMVP		0.095
Mutation Taster		=95/5	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

hg19: chr19-36120104;