NM_001193532.3:c.187C>T

Variant names:

• chr1-28592698-C-T
• rs1388348968
• NM_001193532.3:c.187C>T

Variant summary

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

The NM_001193532.3(RAB42):​c.187C>T​(p.Arg63Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000813 in 1,229,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: RAB42 NM_001193532.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.683
• Publications: 1 publications found

Genes affected

RAB42 (HGNC:28702): (RAB42, member RAS oncogene family) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in Ras protein signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TAF12 (HGNC:11545): (TATA-box binding protein associated factor 12) Control of transcription by RNA polymerase II involves the basal transcription machinery which is a collection of proteins. These proteins with RNA polymerase II, assemble into complexes which are modulated by transactivator proteins that bind to cis-regulatory elements located adjacent to the transcription start site. Some modulators interact directly with the basal complex, whereas others may act as bridging proteins linking transactivators to the basal transcription factors. Some of these associated factors are weakly attached while others are tightly associated with TBP in the TFIID complex. Among the latter are the TAF proteins. Different TAFs are predicted to mediate the function of distinct transcriptional activators for a variety of gene promoters and RNA polymerases. TAF12 interacts directly with TBP as well as with TAF2I. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2008]

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=0.18983713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193532.3. 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
	RAB42	NM_001193532.3	MANE Select	c.187C>T	p.Arg63Trp	missense	Exon 1 of 2	NP_001180461.1	Q8N4Z0-2
	RAB42	NM_001385188.1		c.187C>T	p.Arg63Trp	missense	Exon 1 of 2	NP_001372117.1
	RAB42	NM_152304.3		c.-107+299C>T		intron	N/A	NP_689517.1	Q8N4Z0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB42	ENST00000465518.3	TSL:2 MANE Select	c.187C>T	p.Arg63Trp	missense	Exon 1 of 2	ENSP00000491546.1	Q8N4Z0-2
	RAB42	ENST00000373826.3	TSL:1	c.-107+299C>T		intron	N/A	ENSP00000362932.3	Q8N4Z0-1
	TAF12	ENST00000688108.1		c.451-2312G>A		intron	N/A	ENSP00000510282.1	A0A8I5KTB6

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151854 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000742 AC: 8 AN: 1077886 Hom.: 0 Cov.: 31 AF XY: 0.00000983 AC XY: 5 AN XY: 508852

African (AFR) AF: 0.00 AC: 0 AN: 22862

American (AMR) AF: 0.00 AC: 0 AN: 8370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14292

East Asian (EAS) AF: 0.0000378 AC: 1 AN: 26450

South Asian (SAS) AF: 0.00 AC: 0 AN: 19472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2924

European-Non Finnish (NFE) AF: 0.00000762 AC: 7 AN: 918864

Other (OTH) AF: 0.00 AC: 0 AN: 43538

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151854 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74148

African (AFR) AF: 0.00 AC: 0 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.13
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.97
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.19	T
PhyloP100		-0.68
PrimateAI	Pathogenic	0.86	D
GERP RS		1.7
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.29
gMVP		0.25
Mutation Taster		=100/0	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: rs1388348968; hg19: chr1-28919210; COSMIC: COSV105305727;