X-106772942-G-T

Variant names:

• chrX-106772942-G-T
• NM_194463.2:c.514G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_194463.2(RNF128):​c.514G>T​(p.Gly172Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF128	NM_194463.2	c.514G>T	p.Gly172Cys	missense_variant	Exon 2 of 7	ENST00000255499.3	NP_919445.1
RNF128	NM_024539.3	c.436G>T	p.Gly146Cys	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.514G>T	p.Gly172Cys	missense_variant	Exon 2 of 7	1	NM_194463.2	ENSP00000255499.2
RNF128	ENST00000324342.7	c.436G>T	p.Gly146Cys	missense_variant	Exon 2 of 7	1		ENSP00000316127.3
RNF128	ENST00000418562.5	c.355G>T	p.Gly119Cys	missense_variant	Exon 3 of 6	5		ENSP00000412610.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.514G>T (p.G172C) alteration is located in exon 2 (coding exon 2) of the RNF128 gene. This alteration results from a G to T substitution at nucleotide position 514, causing the glycine (G) at amino acid position 172 to be replaced by a cysteine (C). 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	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	.;.;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.69, 0.71
MutPred		0.74		.;.;Gain of catalytic residue at M170 (P = 0.0019);
MVP		0.86
MPC		1.1
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.95
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-106016172;