Variant 5-180071626-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 NM_018434.6(RNF130):c.77G>A(p.Arg26Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000445 in 1,349,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000044 ( 0 hom. )

Consequence

RNF130
NM_018434.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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:

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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=0.15654731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF130	NM_018434.6 link	c.77G>A	p.Arg26Gln	missense_variant	1/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1 link	c.77G>A	p.Arg26Gln	missense_variant	1/8		NP_001397758.1
RNF130	NM_001280801.2 link	c.77G>A	p.Arg26Gln	missense_variant	1/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF130	ENST00000521389.6 link	c.77G>A	p.Arg26Gln	missense_variant	1/9	1	NM_018434.6	ENSP00000430237.1	Q86XS8-1
RNF130	ENST00000261947.4 link	c.77G>A	p.Arg26Gln	missense_variant	1/8	1		ENSP00000261947.4	Q86XS8-2
RNF130	ENST00000520911.5 link	n.77G>A		non_coding_transcript_exon_variant	1/9	1		ENSP00000430999.1	A0A0C4DGE2
RNF130	ENST00000522208.6 link	c.77G>A	p.Arg26Gln	missense_variant	1/8	5		ENSP00000429509.1	E5RI87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000445

AC:

AN:

1349742

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

670966

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000320

Gnomad4 SAS exome

AF:

0.0000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000379

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000169

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

Mar 07, 2024

The c.77G>A (p.R26Q) alteration is located in exon 1 (coding exon 1) of the RNF130 gene. This alteration results from a G to A substitution at nucleotide position 77, causing the arginine (R) at amino acid position 26 to be replaced by a glutamine (Q). 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

0.090

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

.;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.11

.;B;.

Vest4

0.20

MutPred

0.38

Gain of catalytic residue at R26 (P = 0.0784);Gain of catalytic residue at R26 (P = 0.0784);Gain of catalytic residue at R26 (P = 0.0784);

MVP

0.29

MPC

0.84

ClinPred

0.12

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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