Variant 5-179966812-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018434.6(RNF130):c.1144G>T(p.Val382Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RNF130
NM_018434.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF130	NM_018434.6 link	c.1144G>T	p.Val382Leu	missense_variant	7/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1 link	c.1144G>T	p.Val382Leu	missense_variant	7/8		NP_001397758.1
RNF130	NM_001280801.2 link	c.1144G>T	p.Val382Leu	missense_variant	7/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF130	ENST00000521389.6 link	c.1144G>T	p.Val382Leu	missense_variant	7/9	1	NM_018434.6	ENSP00000430237.1	Q86XS8-1
RNF130	ENST00000520911.5 link	n.*663G>T		non_coding_transcript_exon_variant	7/9	1		ENSP00000430999.1	A0A0C4DGE2
RNF130	ENST00000520911.5 link	n.*663G>T		3_prime_UTR_variant	7/9	1		ENSP00000430999.1	A0A0C4DGE2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461264

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726870

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

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

Oct 12, 2024

The c.1144G>T (p.V382L) alteration is located in exon 7 (coding exon 7) of the RNF130 gene. This alteration results from a G to T substitution at nucleotide position 1144, causing the valine (V) at amino acid position 382 to be replaced by a leucine (L). 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

Pathogenic

0.83

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

.;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M;M

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.85

.;P;.

Vest4

0.65

MutPred

0.26

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.26

MPC

1.7

ClinPred

0.77

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.094

gMVP

0.68

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