rs967219053

Variant names:

• chrX-106726970-A-T
• rs967219053
• NM_194463.2:c.57A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_194463.2(RNF128):​c.57A>T​(p.Arg19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,080,833 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000083 (0 hom. 2 hem.)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.499
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1091426).
• BS2: High Hemizygotes in GnomAdExome4 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.57A>T	p.Arg19Ser	missense	Exon 1 of 7	NP_919445.1	Q8TEB7-1
	RNF128	NM_024539.3		c.406+32562A>T		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.57A>T	p.Arg19Ser	missense	Exon 1 of 7	ENSP00000255499.2	Q8TEB7-1
	RNF128	ENST00000324342.7	TSL:1	c.406+32562A>T		intron	N/A	ENSP00000316127.3	Q8TEB7-2
	RNF128	ENST00000862729.1		c.57A>T	p.Arg19Ser	missense	Exon 1 of 7	ENSP00000532788.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000210 AC: 3 AN: 142933 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000423

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000336

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000833 AC: 9 AN: 1080833 Hom.: 0 Cov.: 31 AF XY: 0.00000568 AC XY: 2 AN XY: 352377

African (AFR) AF: 0.00 AC: 0 AN: 26194

American (AMR) AF: 0.0000308 AC: 1 AN: 32510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18927

East Asian (EAS) AF: 0.00 AC: 0 AN: 29576

South Asian (SAS) AF: 0.00 AC: 0 AN: 51716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3703

European-Non Finnish (NFE) AF: 0.00000959 AC: 8 AN: 834191

Other (OTH) AF: 0.00 AC: 0 AN: 45382

GnomAD4 genome Cov.: 24

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

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	0.23
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.090	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.50
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.25
Sift	Benign	0.41	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.71		Loss of MoRF binding (P = 0.0606)
MVP		0.68
MPC		0.37
ClinPred		0.019	T
GERP RS		1.8
PromoterAI		-0.029	Neutral
Varity_R		0.098
gMVP		0.70
Mutation Taster		=99/1	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: rs967219053; hg19: chrX-105970200;