chr19-35633727-G-T

Variant names:

• chr19-35633727-G-T
• rs1369374361
• NM_024321.5:c.725G>T

Variant summary

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

The NM_024321.5(RBM42):​c.725G>T​(p.Gly242Val) 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. G242A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM42 NM_024321.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• 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 2 ACMG points.

• 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.725G>T	p.Gly242Val	missense_variant	Exon 7 of 10	ENST00000262633.9	NP_077297.2
RBM42	NM_001319113.2	c.638G>T	p.Gly213Val	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.725G>T	p.Gly242Val	missense_variant	Exon 7 of 10	1	NM_024321.5	ENSP00000262633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 117256 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1334418 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 654846

African (AFR) AF: 0.00 AC: 0 AN: 26858

American (AMR) AF: 0.00 AC: 0 AN: 24140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18882

East Asian (EAS) AF: 0.00 AC: 0 AN: 33730

South Asian (SAS) AF: 0.00 AC: 0 AN: 66402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056280

Other (OTH) AF: 0.00 AC: 0 AN: 54692

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;T;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	T;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.;.;.
PhyloP100		3.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.020	.;N;.;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.0020	.;D;.;.;.
Sift4G	Benign	0.54	T;T;T;T;T
Polyphen		1.0	D;B;.;.;.
Vest4		0.79
MVP		0.31
MPC		0.35
ClinPred		0.80	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.091
gMVP		0.46
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1369374361; hg19: chr19-36124629;