chr19-35633088-T-G

Variant names:

• chr19-35633088-T-G
• rs150942017
• NM_024321.5:c.520T>G

Variant summary

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

The NM_024321.5(RBM42):​c.520T>G​(p.Ser174Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,612,806 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 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: RBM42 NM_024321.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783
• 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=0.108995944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM42	NM_024321.5	c.520T>G	p.Ser174Ala	missense_variant	Exon 6 of 10	ENST00000262633.9	NP_077297.2
RBM42	NM_001319113.2	c.443-10T>G		intron_variant	Intron 4 of 8		NP_001306042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM42	ENST00000262633.9	c.520T>G	p.Ser174Ala	missense_variant	Exon 6 of 10	1	NM_024321.5	ENSP00000262633.3

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 251032 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000618

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: 0.0000617

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1460800 Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62 AN XY: 726708

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000141 AC: 157 AN: 1111076

Other (OTH) AF: 0.0000497 AC: 3 AN: 60350

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74238

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.0000642

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520T>G (p.S174A) alteration is located in exon 6 (coding exon 6) of the RBM42 gene. This alteration results from a T to G substitution at nucleotide position 520, causing the serine (S) at amino acid position 174 to be replaced by an alanine (A). 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	0.077
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		0.78
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.53	N;.
REVEL	Benign	0.047
Sift	Benign	0.37	T;.
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;.
Vest4		0.24
MVP		0.29
MPC		0.24
ClinPred		0.024	T
GERP RS		2.9
Varity_R		0.032
gMVP		0.11
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150942017; hg19: chr19-36123990;