X-106694345-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 9/13 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

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

Verdict is Benign. Variant got -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 id is 1206019.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-106694345-G-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF128	NM_024539.3	c.343G>A	p.Asp115Asn	missense_variant	Exon 1 of 7		NP_078815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF128	ENST00000324342.7	c.343G>A	p.Asp115Asn	missense_variant	Exon 1 of 7	1		ENSP00000316127.3
RNF128	ENST00000418562.5	c.262G>A	p.Asp88Asn	missense_variant	Exon 2 of 6	5		ENSP00000412610.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000113 AC: 2 AN: 177548 Hom.: 0 AF XY: 0.0000160 AC XY: 1 AN XY: 62582

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000155

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.91	T
PROVEAN	Benign	0.44	N;N
REVEL	Benign	0.054
Sift	Benign	0.34	T;T
Sift4G	Benign	0.34	T;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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs773333989; hg19: chrX-105937575;