X-106773040-T-A

Position:

• chrX-106773040-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194463.2(RNF128):​c.612T>A​(p.Asn204Lys) 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. 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: 0.681

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37052327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF128	NM_194463.2	c.612T>A	p.Asn204Lys	missense_variant	2/7	ENST00000255499.3	NP_919445.1
RNF128	NM_024539.3	c.534T>A	p.Asn178Lys	missense_variant	2/7		NP_078815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF128	ENST00000255499.3	c.612T>A	p.Asn204Lys	missense_variant	2/7	1	NM_194463.2	ENSP00000255499	P2
RNF128	ENST00000324342.7	c.534T>A	p.Asn178Lys	missense_variant	2/7	1		ENSP00000316127	A1
RNF128	ENST00000418562.5	c.453T>A	p.Asn151Lys	missense_variant	3/6	5		ENSP00000412610

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000756

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

Jul 19, 2023

The c.612T>A (p.N204K) alteration is located in exon 2 (coding exon 2) of the RNF128 gene. This alteration results from a T to A substitution at nucleotide position 612, causing the asparagine (N) at amino acid position 204 to be replaced by a lysine (K). 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	0.96
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	.;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0, 0.89	.;D;P
Vest4		0.71, 0.77
MutPred		0.63		.;.;Gain of methylation at N204 (P = 0.0022);
MVP		0.51
MPC		1.2
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.78
gMVP		0.88

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: rs1930403174; hg19: chrX-106016270;