5-179966818-T-A

Position:

• chr5-179966818-T-A

Variant summary

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

The NM_018434.6(RNF130):​c.1138A>T​(p.Ile380Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF130 NM_018434.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.53

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF130	NM_018434.6	c.1138A>T	p.Ile380Phe	missense_variant	7/9	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1	c.1138A>T	p.Ile380Phe	missense_variant	7/8		NP_001397758.1
RNF130	NM_001280801.2	c.1138A>T	p.Ile380Phe	missense_variant	7/8		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF130	ENST00000521389.6	c.1138A>T	p.Ile380Phe	missense_variant	7/9	1	NM_018434.6	ENSP00000430237.1
RNF130	ENST00000520911.5	n.*657A>T		non_coding_transcript_exon_variant	7/9	1		ENSP00000430999.1
RNF130	ENST00000520911.5	n.*657A>T		3_prime_UTR_variant	7/9	1		ENSP00000430999.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jun 16, 2024

The c.1138A>T (p.I380F) alteration is located in exon 7 (coding exon 7) of the RNF130 gene. This alteration results from a A to T substitution at nucleotide position 1138, causing the isoleucine (I) at amino acid position 380 to be replaced by a phenylalanine (F). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.20	.;T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	.;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.96	T;T;T
Polyphen		0.16	.;B;.
Vest4		0.73
MutPred		0.35		Loss of methylation at K384 (P = 0.0899);Loss of methylation at K384 (P = 0.0899);Loss of methylation at K384 (P = 0.0899);
MVP		0.22
MPC		2.0
ClinPred		0.80	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.75

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: chr5-179393818;