X-106785126-A-G

Position:

• chrX-106785126-A-G

Variant summary

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

The NM_194463.2(RNF128):​c.794A>G​(p.Gln265Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000188 in 1,065,466 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: 22)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

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=0.08162296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF128	NM_194463.2	c.794A>G	p.Gln265Arg	missense_variant	3/7	ENST00000255499.3	NP_919445.1
RNF128	NM_024539.3	c.716A>G	p.Gln239Arg	missense_variant	3/7		NP_078815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF128	ENST00000255499.3	c.794A>G	p.Gln265Arg	missense_variant	3/7	1	NM_194463.2	ENSP00000255499	P2
RNF128	ENST00000324342.7	c.716A>G	p.Gln239Arg	missense_variant	3/7	1		ENSP00000316127	A1
RNF128	ENST00000418562.5	c.635A>G	p.Gln212Arg	missense_variant	4/6	5		ENSP00000412610

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000188 AC: 2 AN: 1065466 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 339920

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000242

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

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

Apr 12, 2024

The c.794A>G (p.Q265R) alteration is located in exon 3 (coding exon 3) of the RNF128 gene. This alteration results from a A to G substitution at nucleotide position 794, causing the glutamine (Q) at amino acid position 265 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0049	T;.;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.37	.;.;N
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.42	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.045, 0.0010	.;B;B
Vest4		0.21, 0.17
MutPred		0.27		.;.;Gain of MoRF binding (P = 0.0382);
MVP		0.26
MPC		0.48
ClinPred		0.19	T
GERP RS		4.3
Varity_R		0.092
gMVP		0.55

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-106028356;