Genetic Variant RNF128:c.-17A>G (chrX-106693986-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024539.3(RNF128):c.-17A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000095 in 1,052,747 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.5e-7 ( 0 hom. 1 hem. )

Consequence

RNF128
NM_024539.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Variant links:

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]

RNF128 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF128	NM_024539.3 link	c.-17A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7		NP_078815.3	Q8TEB7-2
RNF128	NM_024539.3 link	c.-17A>G		5_prime_UTR_variant	Exon 1 of 7		NP_078815.3	Q8TEB7-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
RNF128	ENST00000324342 link	c.-17A>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000324342 link	c.-17A>G	5_prime_UTR_variant	Exon 1 of 7	1	ENSP00000316127.3	Q8TEB7-2
RNF128	ENST00000418562.5 link	c.-11-87A>G	intron_variant	Intron 1 of 5	5	ENSP00000412610.1	Q5JSK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.50e-7

AC:

AN:

1052747

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

334555

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.2

DANN

Benign

0.73

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over