5-179980199-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.695G>A(p.Arg232His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000607 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: RNF130 NM_018434.6 missense, splice_region
• Scores: Splicing: ADA: 0.1791
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.64

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]

LOC124901150 (HGNC:):

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=0.24681473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF130	NM_018434.6	c.695G>A	p.Arg232His	missense_variant, splice_region_variant	4/9	ENST00000521389.6
LOC124901150	XR_007059084.1	n.2266C>T		non_coding_transcript_exon_variant	2/2
RNF130	NM_001410829.1	c.695G>A	p.Arg232His	missense_variant, splice_region_variant	4/8
RNF130	NM_001280801.2	c.695G>A	p.Arg232His	missense_variant, splice_region_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF130	ENST00000521389.6	c.695G>A	p.Arg232His	missense_variant, splice_region_variant	4/9	1	NM_018434.6	P4
	ENST00000649184.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152060 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251414 Hom.: 0 AF XY: 0.0000294 AC XY: 4 AN XY: 135886

Gnomad AFR exome AF: 0.0000615

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000588 AC: 86 AN: 1461646 Hom.: 0 Cov.: 30 AF XY: 0.0000550 AC XY: 40 AN XY: 727148

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

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: 0.0000738

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152060 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74264

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.00

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

May 04, 2023

The c.695G>A (p.R232H) alteration is located in exon 4 (coding exon 4) of the RNF130 gene. This alteration results from a G to A substitution at nucleotide position 695, causing the arginine (R) at amino acid position 232 to be replaced by a histidine (H). 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	0.31
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	29
Dann	Uncertain	1.0
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.037	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.94	.;P;.
Vest4		0.34
MutPred		0.48		Loss of MoRF binding (P = 0.0421);Loss of MoRF binding (P = 0.0421);Loss of MoRF binding (P = 0.0421);
MVP		0.32
MPC		1.0
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.23
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Benign	0.34
SpliceAI score (max)		0.010		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: rs751865376; hg19: chr5-179407199; COSMIC: COSV56148332; COSMIC: COSV56148332;