12-120534870-G-C

Position:

• chr12-120534870-G-C

Variant summary

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

The NM_014868.5(RNF10):​c.59G>C​(p.Gly20Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

Genes affected

RNF10 (HGNC:10055): (ring finger protein 10) The protein encoded by this gene contains a ring finger motif, which is known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. EST data suggests the existence of multiple alternatively spliced transcript variants, however, their full length nature is not known. [provided by RefSeq, Jul 2008]

LOC128071547 (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=0.17333382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF10	NM_014868.5	c.59G>C	p.Gly20Ala	missense_variant	1/17	ENST00000325954.9	NP_055683.3
LOC128071547	NM_001414895.1	c.174G>C	p.Arg58=	synonymous_variant	1/1	ENST00000675818.1	NP_001401824.1
RNF10	NM_001330474.2	c.59G>C	p.Gly20Ala	missense_variant	1/17		NP_001317403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF10	ENST00000325954.9	c.59G>C	p.Gly20Ala	missense_variant	1/17	1	NM_014868.5	ENSP00000322242	P1
	ENST00000675818.1	c.174G>C	p.Arg58=	synonymous_variant	1/1		NM_001414895.1	ENSP00000502390	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 15, 2024

The c.59G>C (p.G20A) alteration is located in exon 1 (coding exon 1) of the RNF10 gene. This alteration results from a G to C substitution at nucleotide position 59, causing the glycine (G) at amino acid position 20 to be replaced by an alanine (A). 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	0.078
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	0.52	N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.41	N;D;N
REVEL	Benign	0.25
Sift	Benign	0.073	T;T;D
Sift4G	Benign	0.66	T;D;T
Polyphen		0.36	B;.;.
Vest4		0.089
MutPred		0.13		Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);
MVP		0.63
MPC		0.36
ClinPred		0.28	T
GERP RS		4.1
Varity_R		0.076
gMVP		0.15

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: rs1320785944; hg19: chr12-120972673;