Genetic Variant RNF10:p.Arg62Leu (chr12-120546432-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014868.5(RNF10):c.185G>T(p.Arg62Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,398 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R62C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 1 hom. )

Consequence

RNF10
NM_014868.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.14

Publications

2 publications found

Variant links:

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]

RNF10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	NM_014868.5	MANE Select	c.185G>T	p.Arg62Leu	missense	Exon 2 of 17	NP_055683.3
	RNF10	NM_001330474.2		c.185G>T	p.Arg62Leu	missense	Exon 2 of 17	NP_001317403.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RNF10	ENST00000325954.9	TSL:1 MANE Select	c.185G>T	p.Arg62Leu	missense	Exon 2 of 17	ENSP00000322242.4
RNF10	ENST00000413266.6	TSL:5	c.185G>T	p.Arg62Leu	missense	Exon 2 of 17	ENSP00000415682.2
RNF10	ENST00000537997.1	TSL:4	c.35G>T	p.Arg12Leu	missense	Exon 3 of 4	ENSP00000443235.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251034

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461398

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111840

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.7

PhyloP100

9.1

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0030

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.85

MutPred

0.29

Loss of methylation at K66 (P = 0.059)

MVP

0.84

MPC

0.84

ClinPred

0.86

GERP RS

4.1

Varity_R

0.53

gMVP

0.50

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over