12-120562975-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014868.5(RNF10):c.1159G>A(p.Gly387Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,040 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00055 ( 9 hom. )

Consequence

RNF10
NM_014868.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.17

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005201936).

BP6

Variant 12-120562975-G-A is Benign according to our data. Variant chr12-120562975-G-A is described in ClinVar as [Benign]. Clinvar id is 784474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00548 (835/152264) while in subpopulation AFR AF= 0.0186 (774/41528). AF 95% confidence interval is 0.0175. There are 5 homozygotes in gnomad4. There are 409 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF10	NM_014868.5 link	c.1159G>A	p.Gly387Arg	missense_variant	Exon 8 of 17	ENST00000325954.9	NP_055683.3	Q8N5U6-1A0A024RBP0
RNF10	NM_001330474.2 link	c.1159G>A	p.Gly387Arg	missense_variant	Exon 8 of 17		NP_001317403.1	Q8N5U6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF10	ENST00000325954.9 link	c.1159G>A	p.Gly387Arg	missense_variant	Exon 8 of 17	1	NM_014868.5	ENSP00000322242.4		Q8N5U6-1

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

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:

0.000162

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00146

AC:

367

AN:

251476

Hom.:

AF XY:

0.00118

AC XY:

161

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000553

AC:

809

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

353

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00548

AC:

835

AN:

152264

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.000866

Hom.:

Bravo

AF:

0.00594

ESP6500AA

AF:

0.0184

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00183

AC:

222

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0083

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.20

N;.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.46

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.41

T;D;T

Sift4G

Benign

0.39

T;D;T

Polyphen

0.0020

B;.;B

Vest4

0.30

MutPred

0.36

Gain of MoRF binding (P = 0.006);.;Gain of MoRF binding (P = 0.006);

MVP

0.58

MPC

0.23

ClinPred

0.013

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.066

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over