chrX-106772930-G-A

Variant names:

• chrX-106772930-G-A
• rs1053005721
• NM_194463.2:c.502G>A

Variant summary

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

The NM_194463.2(RNF128):​c.502G>A​(p.Ala168Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40
• Publications: 0 publications found

Genes affected

RNF128 (HGNC:21153): (ring finger protein 128) The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. This protein contains a RING zinc-finger motif and has been shown to possess E3 ubiquitin ligase activity. Expression of this gene in retrovirally transduced T cell hybridoma significantly inhibits activation-induced IL2 and IL4 cytokine production. Induced expression of this gene was observed in anergic CD4(+) T cells, which suggested a role in the induction of anergic phenotype. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194463.2. 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
	RNF128	NM_194463.2	MANE Select	c.502G>A	p.Ala168Thr	missense	Exon 2 of 7	NP_919445.1	Q8TEB7-1
	RNF128	NM_024539.3		c.424G>A	p.Ala142Thr	missense	Exon 2 of 7	NP_078815.3	Q8TEB7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF128	ENST00000255499.3	TSL:1 MANE Select	c.502G>A	p.Ala168Thr	missense	Exon 2 of 7	ENSP00000255499.2	Q8TEB7-1
	RNF128	ENST00000324342.7	TSL:1	c.424G>A	p.Ala142Thr	missense	Exon 2 of 7	ENSP00000316127.3	Q8TEB7-2
	RNF128	ENST00000862729.1		c.496G>A	p.Ala166Thr	missense	Exon 2 of 7	ENSP00000532788.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.62		Loss of sheet (P = 0.1158)
MVP		0.53
MPC		0.93
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.72
gMVP		0.97
Mutation Taster		=47/53	disease causing

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: rs1053005721; hg19: chrX-106016160;