Variant 5-179966851-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000521389.6(RNF130):c.1105G>A(p.Gly369Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000055 ( 0 hom. )

Consequence

RNF130
ENST00000521389.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18029508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF130	NM_018434.6 linkuse as main transcript	c.1105G>A	p.Gly369Arg	missense_variant	7/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1 linkuse as main transcript	c.1105G>A	p.Gly369Arg	missense_variant	7/8		NP_001397758.1
RNF130	NM_001280801.2 linkuse as main transcript	c.1105G>A	p.Gly369Arg	missense_variant	7/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF130	ENST00000521389.6 linkuse as main transcript	c.1105G>A	p.Gly369Arg	missense_variant	7/9	1	NM_018434.6	ENSP00000430237	P4	Q86XS8-1
RNF130	ENST00000261947.4 linkuse as main transcript	c.1105G>A	p.Gly369Arg	missense_variant	7/8	1		ENSP00000261947	A2	Q86XS8-2
RNF130	ENST00000520911.5 linkuse as main transcript	c.*624G>A		3_prime_UTR_variant, NMD_transcript_variant	7/9	1		ENSP00000430999
RNF130	ENST00000522208.6 linkuse as main transcript	c.1105G>A	p.Gly369Arg	missense_variant	7/8	5		ENSP00000429509	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251420

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135900

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727240

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:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jan 26, 2023

The c.1105G>A (p.G369R) alteration is located in exon 7 (coding exon 7) of the RNF130 gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the glycine (G) at amino acid position 369 to be replaced by an arginine (R). 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

0.26

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;T;.

Eigen

Benign

0.0066

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.1

.;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.063

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.56

.;P;.

Vest4

0.52

MutPred

0.20

Gain of phosphorylation at T372 (P = 0.1058);Gain of phosphorylation at T372 (P = 0.1058);Gain of phosphorylation at T372 (P = 0.1058);

MVP

0.11

MPC

0.94

ClinPred

0.30

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.090

gMVP

0.52

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