rs1053005721

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 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
RNF128	NM_194463.2	c.502G>A	p.Ala168Thr	missense_variant	Exon 2 of 7	ENST00000255499.3	NP_919445.1
RNF128	NM_024539.3	c.424G>A	p.Ala142Thr	missense_variant	Exon 2 of 7		NP_078815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF128	ENST00000255499.3	c.502G>A	p.Ala168Thr	missense_variant	Exon 2 of 7	1	NM_194463.2	ENSP00000255499.2
RNF128	ENST00000324342.7	c.424G>A	p.Ala142Thr	missense_variant	Exon 2 of 7	1		ENSP00000316127.3
RNF128	ENST00000418562.5	c.343G>A	p.Ala115Thr	missense_variant	Exon 3 of 6	5		ENSP00000412610.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.502G>A (p.A168T) alteration is located in exon 2 (coding exon 2) of the RNF128 gene. This alteration results from a G to A substitution at nucleotide position 502, causing the alanine (A) at amino acid position 168 to be replaced by a threonine (T). 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	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;.;D
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0, 0.97	.;D;D
Vest4		0.64, 0.65
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1053005721; hg19: chrX-106016160;