chrX-106694345-G-A

Variant names:

• chrX-106694345-G-A
• rs773333989
• ENST00000324342.7:c.343G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_024539.3(RNF128):​c.343G>A​(p.Asp115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,094,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000013 (0 hom. 7 hem.)
• Consequence: RNF128 NM_024539.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.243
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11309904).
• BP6: Variant X-106694345-G-A is Benign according to our data. Variant chrX-106694345-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1206019.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024539.3. 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_024539.3		c.343G>A	p.Asp115Asn	missense	Exon 1 of 7	NP_078815.3	Q8TEB7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF128	ENST00000324342.7	TSL:1	c.343G>A	p.Asp115Asn	missense	Exon 1 of 7	ENSP00000316127.3	Q8TEB7-2
	RNF128	ENST00000418562.5	TSL:5	c.262G>A	p.Asp88Asn	missense	Exon 2 of 6	ENSP00000412610.1	Q5JSK4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000113 AC: 2 AN: 177548 AF XY: 0.0000160

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: 0.0000251

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 14 AN: 1094631 Hom.: 0 Cov.: 30 AF XY: 0.0000194 AC XY: 7 AN XY: 360323

African (AFR) AF: 0.00 AC: 0 AN: 26281

American (AMR) AF: 0.00 AC: 0 AN: 34799

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19134

East Asian (EAS) AF: 0.00 AC: 0 AN: 30183

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53155

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4110

European-Non Finnish (NFE) AF: 0.0000155 AC: 13 AN: 840580

Other (OTH) AF: 0.00 AC: 0 AN: 45975

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0035	T
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.24
PROVEAN	Benign	0.44	N
REVEL	Benign	0.054
Sift	Benign	0.34	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.56		Loss of stability (P = 0.0406)
MVP		0.25
ClinPred		0.024	T
GERP RS		3.4
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs773333989; hg19: chrX-105937575;