NM_194463.2:c.44G>A

Variant names:

• chrX-106726957-G-A
• rs771028080
• NM_194463.2:c.44G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_194463.2(RNF128):​c.44G>A​(p.Cys15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000926 in 1,187,864 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.0000056 (0 hom. 1 hem.)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.202
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06688091).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

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.44G>A	p.Cys15Tyr	missense	Exon 1 of 7	NP_919445.1	Q8TEB7-1
	RNF128	NM_024539.3		c.406+32549G>A		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.44G>A	p.Cys15Tyr	missense	Exon 1 of 7	ENSP00000255499.2	Q8TEB7-1
	RNF128	ENST00000324342.7	TSL:1	c.406+32549G>A		intron	N/A	ENSP00000316127.3	Q8TEB7-2
	RNF128	ENST00000862729.1		c.44G>A	p.Cys15Tyr	missense	Exon 1 of 7	ENSP00000532788.1

Frequencies

GnomAD3 genomes AF: 0.0000441 AC: 5 AN: 113505 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000150 AC: 2 AN: 133130 AF XY: 0.0000247

Gnomad AFR exome AF: 0.000119

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000286

GnomAD4 exome AF: 0.00000558 AC: 6 AN: 1074359 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 1 AN XY: 349457

African (AFR) AF: 0.0000384 AC: 1 AN: 26050

American (AMR) AF: 0.0000637 AC: 2 AN: 31374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18825

East Asian (EAS) AF: 0.00 AC: 0 AN: 29175

South Asian (SAS) AF: 0.00 AC: 0 AN: 51147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3471

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831061

Other (OTH) AF: 0.0000665 AC: 3 AN: 45140

GnomAD4 genome AF: 0.0000441 AC: 5 AN: 113505 Hom.: 0 Cov.: 24 AF XY: 0.0000561 AC XY: 2 AN XY: 35625

African (AFR) AF: 0.00 AC: 0 AN: 31353

American (AMR) AF: 0.000459 AC: 5 AN: 10891

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2663

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53392

Other (OTH) AF: 0.00 AC: 0 AN: 1534

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000128

ExAC AF: 0.00000855 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.20
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.11	T
Polyphen		0.031	B
Vest4		0.28
MutPred		0.31		Loss of disorder (P = 0.0467)
MVP		0.59
MPC		0.56
ClinPred		0.097	T
GERP RS		3.1
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.34
gMVP		0.74
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: rs771028080; hg19: chrX-105970187;