X-106726930-G-C

Position:

• chrX-106726930-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194463.2(RNF128):​c.17G>C​(p.Gly6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1944566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF128	NM_194463.2	c.17G>C	p.Gly6Ala	missense_variant	1/7	ENST00000255499.3	NP_919445.1
RNF128	NM_024539.3	c.406+32522G>C		intron_variant			NP_078815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF128	ENST00000255499.3	c.17G>C	p.Gly6Ala	missense_variant	1/7	1	NM_194463.2	ENSP00000255499	P2
RNF128	ENST00000324342.7	c.406+32522G>C		intron_variant		1		ENSP00000316127	A1
RNF128	ENST00000418562.5	c.325+32522G>C		intron_variant		5		ENSP00000412610

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2023

The c.17G>C (p.G6A) alteration is located in exon 1 (coding exon 1) of the RNF128 gene. This alteration results from a G to C substitution at nucleotide position 17, causing the glycine (G) at amino acid position 6 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	0.080
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.080	T
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.54	D;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.076
Sift	Benign	0.14	T
Sift4G	Benign	0.16	T
Polyphen		0.64	P
Vest4		0.19
MutPred		0.099		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.56
MPC		0.35
ClinPred		0.16	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.080
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-105970160;