NM_194463.2:c.529A>G

Variant names:

• chrX-106772957-A-G
• rs755237340
• NM_194463.2:c.529A>G

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.529A>G​(p.Thr177Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000811 in 1,097,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 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: not found (cov: 23)
  • Exomes 𝑓: 0.000081 (0 hom. 27 hem.)
• Consequence: RNF128 NM_194463.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24967575).
• BS2: High Hemizygotes in GnomAdExome4 at 27 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.529A>G	p.Thr177Ala	missense	Exon 2 of 7	NP_919445.1	Q8TEB7-1
	RNF128	NM_024539.3		c.451A>G	p.Thr151Ala	missense	Exon 2 of 7	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.529A>G	p.Thr177Ala	missense	Exon 2 of 7	ENSP00000255499.2	Q8TEB7-1
	RNF128	ENST00000324342.7	TSL:1	c.451A>G	p.Thr151Ala	missense	Exon 2 of 7	ENSP00000316127.3	Q8TEB7-2
	RNF128	ENST00000862729.1		c.523A>G	p.Thr175Ala	missense	Exon 2 of 7	ENSP00000532788.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000219 AC: 4 AN: 182327 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

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: 0.0000491

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000811 AC: 89 AN: 1097060 Hom.: 0 Cov.: 29 AF XY: 0.0000745 AC XY: 27 AN XY: 362468

African (AFR) AF: 0.00 AC: 0 AN: 26374

American (AMR) AF: 0.00 AC: 0 AN: 35170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19369

East Asian (EAS) AF: 0.00 AC: 0 AN: 30190

South Asian (SAS) AF: 0.00 AC: 0 AN: 53976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.000106 AC: 89 AN: 841269

Other (OTH) AF: 0.00 AC: 0 AN: 46059

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.000297

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	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.53	T
Polyphen		0.31	B
Vest4		0.34
MutPred		0.47		Loss of helix (P = 0.0167)
MVP		0.51
MPC		0.42
ClinPred		0.13	T
GERP RS		5.8
Varity_R		0.37
gMVP		0.69
Mutation Taster		=77/23	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: rs755237340; hg19: chrX-106016187; COSMIC: COSV99718218;