5-180071695-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018434.6(RNF130):c.8G>A(p.Cys3Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000817 in 1,224,546 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: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: RNF130 NM_018434.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.374

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]

ACMG classification

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=0.08580598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF130	NM_018434.6	c.8G>A	p.Cys3Tyr	missense_variant	1/9	ENST00000521389.6
RNF130	NM_001410829.1	c.8G>A	p.Cys3Tyr	missense_variant	1/8
RNF130	NM_001280801.2	c.8G>A	p.Cys3Tyr	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF130	ENST00000521389.6	c.8G>A	p.Cys3Tyr	missense_variant	1/9	1	NM_018434.6	P4
RNF130	ENST00000261947.4	c.8G>A	p.Cys3Tyr	missense_variant	1/8	1		A2
RNF130	ENST00000520911.5	c.8G>A	p.Cys3Tyr	missense_variant, NMD_transcript_variant	1/9	1
RNF130	ENST00000522208.6	c.8G>A	p.Cys3Tyr	missense_variant	1/8	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.17e-7 AC: 1 AN: 1224546 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 601878

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: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 08, 2023

The c.8G>A (p.C3Y) 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 8, causing the cysteine (C) at amino acid position 3 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	19
Dann	Uncertain	0.97
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.70	N;N;N
REVEL	Benign	0.047
Sift	Benign	0.068	T;T;T
Sift4G	Uncertain	0.043	D;D;T
Polyphen		0.0	.;B;.
Vest4		0.20
MutPred		0.56		Gain of MoRF binding (P = 0.065);Gain of MoRF binding (P = 0.065);Gain of MoRF binding (P = 0.065);
MVP		0.068
MPC		1.1
ClinPred		0.097	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-179498695;