X-106727205-C-G

Variant names:

• chrX-106727205-C-G
• rs890212416
• NM_194463.2:c.292C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194463.2(RNF128):​c.292C>G​(p.Pro98Ala) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P98T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25732338).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194463.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF128	NM_194463.2	MANE Select	c.292C>G	p.Pro98Ala	missense	Exon 1 of 7	NP_919445.1	Q8TEB7-1
	RNF128	NM_024539.3		c.406+32797C>G		intron	N/A	NP_078815.3	Q8TEB7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF128	ENST00000255499.3	TSL:1 MANE Select	c.292C>G	p.Pro98Ala	missense	Exon 1 of 7	ENSP00000255499.2	Q8TEB7-1
	RNF128	ENST00000324342.7	TSL:1	c.406+32797C>G		intron	N/A	ENSP00000316127.3	Q8TEB7-2
	RNF128	ENST00000862729.1		c.292C>G	p.Pro98Ala	missense	Exon 1 of 7	ENSP00000532788.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.49	T
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.081
Sift	Benign	0.057	T
Sift4G	Benign	0.27	T
Polyphen		0.0060	B
Vest4		0.11
MutPred		0.75		Loss of stability (P = 0.1668)
MVP		0.24
MPC		0.32
ClinPred		0.13	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.84
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs890212416; hg19: chrX-105970435;