5-180071634-C-G

Variant summary

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

The NM_018434.6(RNF130):c.69G>C(p.Trp23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,346,062 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: 0.000010 ( 0 hom. )

Consequence

RNF130
NM_018434.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

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=0.1392281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF130	NM_018434.6 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant	1/9	ENST00000521389.6
RNF130	NM_001410829.1 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant	1/8
RNF130	NM_001280801.2 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF130	ENST00000521389.6 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant	1/9	1	NM_018434.6	P4	Q86XS8-1
RNF130	ENST00000261947.4 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant	1/8	1		A2	Q86XS8-2
RNF130	ENST00000520911.5 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant, NMD_transcript_variant	1/9	1
RNF130	ENST00000522208.6 linkuse as main transcript	c.69G>C	p.Trp23Cys	missense_variant	1/8	5		A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000879

AC:

AN:

147848

Hom.:

AF XY:

0.0000471

AC XY:

AN XY:

84866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000455

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:

0.00

Gnomad OTH exome

AF:

0.000895

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1346062

Hom.:

Cov.:

AF XY:

0.00000748

AC XY:

AN XY:

668876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

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:

9.48e-7

Gnomad4 OTH exome

AF:

0.0000365

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000681

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

Aug 17, 2021

The c.69G>C (p.W23C) alteration is located in exon 1 (coding exon 1) of the RNF130 gene. This alteration results from a G to C substitution at nucleotide position 69, causing the tryptophan (W) at amino acid position 23 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Benign

0.76

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.82

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.090

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.55

.;P;.

Vest4

0.40

MutPred

0.60

Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);

MVP

0.043

MPC

1.1

ClinPred

0.035

GERP RS

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.42

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