NM_024321.5:c.761C>G

Variant names:

• chr19-35633763-C-G
• rs371819218
• NM_024321.5:c.761C>G

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.761C>G​(p.Ala254Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. A254V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: RBM42 NM_024321.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661
• 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=0.17278561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM42	NM_024321.5	c.761C>G	p.Ala254Gly	missense_variant	Exon 7 of 10	ENST00000262633.9	NP_077297.2
RBM42	NM_001319113.2	c.674C>G	p.Ala225Gly	missense_variant	Exon 6 of 9		NP_001306042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM42	ENST00000262633.9	c.761C>G	p.Ala254Gly	missense_variant	Exon 7 of 10	1	NM_024321.5	ENSP00000262633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333118 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 654602

African (AFR) AF: 0.00 AC: 0 AN: 27250

American (AMR) AF: 0.00 AC: 0 AN: 24990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19236

East Asian (EAS) AF: 0.00 AC: 0 AN: 33650

South Asian (SAS) AF: 0.0000149 AC: 1 AN: 66924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055310

Other (OTH) AF: 0.00 AC: 0 AN: 54734

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	.;T;T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.80	T;D;D;T;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	.;N;.;.;.
PhyloP100		0.66
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.75	.;N;.;.;.
REVEL	Benign	0.037
Sift	Uncertain	0.029	.;D;.;.;.
Sift4G	Benign	0.41	T;T;T;T;T
Polyphen		0.82	P;P;.;.;.
Vest4		0.43
MutPred		0.24		.;Gain of catalytic residue at L259 (P = 0.205);.;.;.;
MVP		0.24
MPC		0.28
ClinPred		0.21	T
GERP RS		3.2
Varity_R		0.071
gMVP		0.32
Mutation Taster		=86/14	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: rs371819218; hg19: chr19-36124665;