5-180071657-C-A

Position:

• chr5-180071657-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018434.6(RNF130):​c.46G>T​(p.Ala16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000077 in 1,299,240 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: 7.7e-7 (0 hom.)
• Consequence: RNF130 NM_018434.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.713

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27725774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF130	NM_018434.6	c.46G>T	p.Ala16Ser	missense_variant	1/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1	c.46G>T	p.Ala16Ser	missense_variant	1/8		NP_001397758.1
RNF130	NM_001280801.2	c.46G>T	p.Ala16Ser	missense_variant	1/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF130	ENST00000521389.6	c.46G>T	p.Ala16Ser	missense_variant	1/9	1	NM_018434.6	ENSP00000430237	P4
RNF130	ENST00000261947.4	c.46G>T	p.Ala16Ser	missense_variant	1/8	1		ENSP00000261947	A2
RNF130	ENST00000520911.5	c.46G>T	p.Ala16Ser	missense_variant, NMD_transcript_variant	1/9	1		ENSP00000430999
RNF130	ENST00000522208.6	c.46G>T	p.Ala16Ser	missense_variant	1/8	5		ENSP00000429509	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.70e-7 AC: 1 AN: 1299240 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 642706

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: 0.0000278

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Mar 17, 2023

The c.46G>T (p.A16S) alteration is located in exon 1 (coding exon 1) of the RNF130 gene. This alteration results from a G to T substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	.;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.070
Sift	Benign	0.20	T;T;D
Sift4G	Benign	0.33	T;T;T
Polyphen		0.73	.;P;.
Vest4		0.37
MutPred		0.67		Gain of glycosylation at A16 (P = 0.0681);Gain of glycosylation at A16 (P = 0.0681);Gain of glycosylation at A16 (P = 0.0681);
MVP		0.15
MPC		0.62
ClinPred		0.28	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.36

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

Other links and lift over

dbSNP: rs1361593114; hg19: chr5-179498657;