RNF10 p.Ile138Asn

Variant names:

• chr12-120552557-T-A
• rs370551365
• NM_014868.5:c.413T>A
• RNF10 p.Ile138Asn

Your query was ambiguous. Multiple possible variants found:

• chr12-120552557-T-A
• chr12-120552557-TC-AT

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+3 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 3 classification points (ACMG Germline Pathogenicity v2019). PM2_SupportingPP3_Moderate

The NM_014868.5(RNF10):c.413T>A (p.Ile138Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000954 (AC=154) in the gnomAD database across 1,614,070 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.000109. In-silico predictor (REVEL) classifies this variant as likely damaging/oncogenic. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.63). Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• Publications: 0 publications found

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]

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Uncertain_significance. The variant received 3 points.

• PM2: Rare in gnomAD for AR/unknown gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.000109 — borderline rare for unknown gene (threshold 0.001) — PM2 supporting.
• PP3: Germline meta computational scorer (REVEL/MetaRNN/BayesDel) predicts damaging effect — moderate evidence (PP3); Splicing verdict: not pathogenic.; Germline computational verdict: pathogenic (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_014868.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	NM_014868.5	MANE Select	c.413T>A	p.Ile138Asn	missense	Exon 3 of 17	NP_055683.3
	RNF10	NM_001330474.2		c.413T>A	p.Ile138Asn	missense	Exon 3 of 17	NP_001317403.1	Q8N5U6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	ENST00000325954.9	TSL:1 MANE Select	c.413T>A	p.Ile138Asn	missense	Exon 3 of 17	ENSP00000322242.4	Q8N5U6-1
	RNF10	ENST00000413266.6	TSL:5	c.413T>A	p.Ile138Asn	missense	Exon 3 of 17	ENSP00000415682.2	Q8N5U6-2
	RNF10	ENST00000537997.1	TSL:4	c.263T>A	p.Ile88Asn	missense	Exon 4 of 4	ENSP00000443235.1	F5H5P6

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	0.0000329	5	0	152186	31
GnomAD2 exomes	0.0000358	9		251480
GnomAD4 exome	0.000102	149	0	1461884	31
GnomAD4 genome	0.0000329	5	0	152186	31
TOPMed (Bravo)	0.0000340
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.0000262	1	0	38222
Local & regional cohorts 2 sources Population-specific and national genomic databases
ESP6500 (Exome Variant Server)	0.0000769	1		13006
UK10K	0.000397	3		7562

Showing 8 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.000520 *	5	9622	0.0000959 *	1	10428
BipEx(Bipolar disorder (including schizoaffective))	0.000141	4	28420	0.000208	6	28842
Epi25(Epilepsy)	0.0000477	2	41958	0.0000897	6	66888
SCHEMA(Schizophrenia)	0.0000492	6	121918	0.0000577	11	190682

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	26
AlphaMissense	Pathogenic	-	0.77
BayesDel_addAF	Pathogenic	D	0.25
BayesDel_noAF	Pathogenic	-	0.31
CADD	Pathogenic	-	28
DANN	Uncertain	-	0.99
DEOGEN2	Benign	T	0.10
Eigen	Pathogenic	-	0.68
Eigen_PC	Pathogenic	-	0.69
FATHMM_MKL	Pathogenic	D	0.99
FuncVEP CTI	Benign	-	0.034
GPN-Star LLR	N/A	-	-11
GPN-Star score	N/A	-	11
LIST_S2	Uncertain	D	0.96
M_CAP	Pathogenic	D	0.35
MetaRNN	Pathogenic	D	0.75
MetaSVM	Uncertain	D	0.73
Mutation Taster	N/A	disease causing	42/58
MutationAssessor	Uncertain	M	2.5
PhyloP100	Pathogenic	-	7.6
popEVE	Benign	-	-3.6
PrimateAI	Pathogenic	D	0.85
PROVEAN	Benign	N	-2.2
RBP_binding_hub_radar	N/A	-	0.0
RBP_regulation_power_radar	N/A	-	1.7
REVEL	Pathogenic	-	0.81
Sift	Uncertain	D	0.015
Sift4G	Uncertain	D	0.025
Varity_R	N/A	-	0.38
VESM-3B	Benign	-	-11

Showing 30 of 30 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs370551365;

hg19: chr12-120990360;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar