5-180071461-T-C

Position:

chr5-180071461-T-C

Variant summary

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

The NM_018434.6(RNF130):c.242A>G(p.His81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000402 in 1,242,964 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: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

RNF130
NM_018434.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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=0.10005018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF130	NM_018434.6 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant	1/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant	1/8		NP_001397758.1
RNF130	NM_001280801.2 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant	1/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF130	ENST00000521389.6 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant	1/9	1	NM_018434.6	ENSP00000430237	P4	Q86XS8-1
RNF130	ENST00000261947.4 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant	1/8	1		ENSP00000261947	A2	Q86XS8-2
RNF130	ENST00000520911.5 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant, NMD_transcript_variant	1/9	1		ENSP00000430999
RNF130	ENST00000522208.6 linkuse as main transcript	c.242A>G	p.His81Arg	missense_variant	1/8	5		ENSP00000429509	A1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000343

AC:

AN:

2912

Hom.:

AF XY:

0.000561

AC XY:

AN XY:

1784

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:

0.000789

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000394

AC:

AN:

1091140

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

517528

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:

0.0000444

Gnomad4 OTH exome

AF:

0.0000456

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151824

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

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

Dec 20, 2023

The c.242A>G (p.H81R) alteration is located in exon 1 (coding exon 1) of the RNF130 gene. This alteration results from a A to G substitution at nucleotide position 242, causing the histidine (H) at amino acid position 81 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

0.088

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.19

.;T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.76

T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

.;L;L

MutationTaster

Benign

0.78

N;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.27

.;B;.

Vest4

0.25

MutPred

0.45

Loss of catalytic residue at G82 (P = 0.0572);Loss of catalytic residue at G82 (P = 0.0572);Loss of catalytic residue at G82 (P = 0.0572);

MVP

0.20

MPC

1.0

ClinPred

0.061

GERP RS

2.1

Varity_R

0.075

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