Variant 13-26214167-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005977.4(RNF6):c.1715G>A(p.Arg572Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,144 control chromosomes in the GnomAD database, including 15 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 12 hom. )

Consequence

RNF6
NM_005977.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

RNF6 (HGNC:10069): (ring finger protein 6) The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed. [provided by RefSeq, Jul 2008]

RNF6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003478974).

BP6

Variant 13-26214167-C-T is Benign according to our data. Variant chr13-26214167-C-T is described in ClinVar as [Benign]. Clinvar id is 714576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF6	NM_005977.4 linkuse as main transcript	c.1715G>A	p.Arg572Gln	missense_variant	5/5	ENST00000381588.9	NP_005968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF6	ENST00000381588.9 linkuse as main transcript	c.1715G>A	p.Arg572Gln	missense_variant	5/5	1	NM_005977.4	ENSP00000371000	P1	Q9Y252-1
RNF6	ENST00000346166.7 linkuse as main transcript	c.1715G>A	p.Arg572Gln	missense_variant	5/5	1		ENSP00000342121	P1	Q9Y252-1
RNF6	ENST00000381570.7 linkuse as main transcript	c.1715G>A	p.Arg572Gln	missense_variant	5/5	1		ENSP00000370982	P1	Q9Y252-1
RNF6	ENST00000468480.5 linkuse as main transcript	n.768+1307G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

692

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00196

AC:

493

AN:

251442

Hom.:

AF XY:

0.00185

AC XY:

252

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00527

Gnomad SAS exome

AF:

0.00330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000980

AC:

1432

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000943

AC XY:

686

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00199

Gnomad4 SAS exome

AF:

0.00308

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000373

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.00454

AC:

691

AN:

152252

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

324

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00463

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00532

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00211

AC:

256

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

DANN

Benign

0.88

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.65

.;.;T

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.048

MVP

0.23

MPC

0.34

ClinPred

0.000014

GERP RS

-2.0

Varity_R

0.016

gMVP

0.44

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

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