Variant 5-180071500-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018434.6(RNF130):c.203C>T(p.Ala68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF130
NM_018434.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.889

Variant links:

Genes affected

RNF130 (HGNC:18280): (ring finger protein 130) The protein encoded by this gene contains a RING finger motif and is similar to g1, a Drosophila zinc-finger protein that is expressed in mesoderm and involved in embryonic development. The expression of the mouse counterpart was found to be upregulated in myeloblastic cells following IL3 deprivation, suggesting that this gene may regulate growth factor withdrawal-induced apoptosis of myeloid precursor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RNF130 links:

Genome browser will be placed here

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 (MetaRNN=0.065293044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF130	NM_018434.6 link	c.203C>T	p.Ala68Val	missense_variant	1/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1 link	c.203C>T	p.Ala68Val	missense_variant	1/8		NP_001397758.1
RNF130	NM_001280801.2 link	c.203C>T	p.Ala68Val	missense_variant	1/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF130	ENST00000521389.6 link	c.203C>T	p.Ala68Val	missense_variant	1/9	1	NM_018434.6	ENSP00000430237.1	Q86XS8-1
RNF130	ENST00000261947.4 link	c.203C>T	p.Ala68Val	missense_variant	1/8	1		ENSP00000261947.4	Q86XS8-2
RNF130	ENST00000520911.5 link	n.203C>T		non_coding_transcript_exon_variant	1/9	1		ENSP00000430999.1	A0A0C4DGE2
RNF130	ENST00000522208.6 link	c.203C>T	p.Ala68Val	missense_variant	1/8	5		ENSP00000429509.1	E5RI87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000225

AC:

AN:

44498

Hom.:

AF XY:

0.0000385

AC XY:

AN XY:

25974

show subpopulations

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:

0.0000454

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1153098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

554902

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.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.203C>T (p.A68V) alteration is located in exon 1 (coding exon 1) of the RNF130 gene. This alteration results from a C to T substitution at nucleotide position 203, causing the alanine (A) at amino acid position 68 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.68

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.63

.;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.50

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.091

MutPred

0.26

Loss of ubiquitination at K67 (P = 0.0431);Loss of ubiquitination at K67 (P = 0.0431);Loss of ubiquitination at K67 (P = 0.0431);

MVP

0.043

MPC

0.67

ClinPred

0.088

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.18

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over