NM_024321.5:c.764C>T

Variant names:

• chr19-35633766-C-T
• rs201842352
• NM_024321.5:c.764C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024321.5(RBM42):​c.764C>T​(p.Ala255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,494,208 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: RBM42 NM_024321.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09397301).

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.764C>T	p.Ala255Val	missense	Exon 7 of 10	NP_077297.2
	RBM42	NM_001319113.2		c.677C>T	p.Ala226Val	missense	Exon 6 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.764C>T	p.Ala255Val	missense	Exon 7 of 10	ENSP00000262633.3	Q9BTD8-1
	RBM42	ENST00000588161.5	TSL:1	c.674C>T	p.Ala225Val	missense	Exon 6 of 9	ENSP00000466044.1	Q9BTD8-2
	RBM42	ENST00000943049.1		c.755C>T	p.Ala252Val	missense	Exon 7 of 10	ENSP00000613108.1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000263 AC: 30 AN: 113906 AF XY: 0.000257

Gnomad AFR exome AF: 0.000275

Gnomad AMR exome AF: 0.000129

Gnomad ASJ exome AF: 0.000428

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.0000843

Gnomad NFE exome AF: 0.000430

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000482 AC: 647 AN: 1341998 Hom.: 0 Cov.: 31 AF XY: 0.000458 AC XY: 302 AN XY: 659576

African (AFR) AF: 0.00 AC: 0 AN: 27406

American (AMR) AF: 0.0000387 AC: 1 AN: 25838

Ashkenazi Jewish (ASJ) AF: 0.0000515 AC: 1 AN: 19434

East Asian (EAS) AF: 0.0000295 AC: 1 AN: 33922

South Asian (SAS) AF: 0.0000146 AC: 1 AN: 68390

European-Finnish (FIN) AF: 0.0000216 AC: 1 AN: 46222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5286

European-Non Finnish (NFE) AF: 0.000588 AC: 623 AN: 1060356

Other (OTH) AF: 0.000345 AC: 19 AN: 55144

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74362

African (AFR) AF: 0.0000965 AC: 4 AN: 41464

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000451 Hom.: 0

Bravo AF: 0.000310

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000229 AC: 1

ESP6500EA AF: 0.000586 AC: 5

ExAC AF: 0.000109 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.090
Sift	Uncertain	0.014	D
Sift4G	Benign	0.12	T
Polyphen		0.88	P
Vest4		0.35
MVP		0.25
MPC		0.28
ClinPred		0.029	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.083
gMVP		0.41
Mutation Taster		=90/10	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: rs201842352; hg19: chr19-36124668; COSMIC: COSV52897745; COSMIC: COSV52897745;