NM_005977.4:c.608T>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005977.4(RNF6):c.608T>A(p.Val203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,614,168 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. V203A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0087 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 36 hom. )

Consequence

RNF6
NM_005977.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

esophageal cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RNF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026439428).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00868 (1322/152278) while in subpopulation AFR AF = 0.0171 (710/41560). AF 95% confidence interval is 0.016. There are 9 homozygotes in GnomAd4. There are 627 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF6	NM_005977.4	MANE Select	c.608T>A	p.Val203Glu	missense	Exon 5 of 5	NP_005968.1	A0A024RDP2
RNF6	NM_183043.3		c.608T>A	p.Val203Glu	missense	Exon 5 of 5	NP_898864.1	Q9Y252-1
RNF6	NM_183044.3		c.608T>A	p.Val203Glu	missense	Exon 5 of 5	NP_898865.1	Q9Y252-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF6	ENST00000381588.9	TSL:1 MANE Select	c.608T>A	p.Val203Glu	missense	Exon 5 of 5	ENSP00000371000.4	Q9Y252-1
RNF6	ENST00000346166.7	TSL:1	c.608T>A	p.Val203Glu	missense	Exon 5 of 5	ENSP00000342121.3	Q9Y252-1
RNF6	ENST00000381570.7	TSL:1	c.608T>A	p.Val203Glu	missense	Exon 5 of 5	ENSP00000370982.3	Q9Y252-1

Frequencies

GnomAD3 genomes

AF:

0.00865

AC:

1316

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00826

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00565

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00520

AC:

1307

AN:

251484

AF XY:

0.00475

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00680

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.00510

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00599

AC:

8753

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00566

AC XY:

4118

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0172

AC:

576

AN:

33480

American (AMR)

AF:

0.00210

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00471

AC:

187

AN:

39700

South Asian (SAS)

AF:

0.000128

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00760

AC:

406

AN:

53420

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00632

AC:

7032

AN:

1112010

Other (OTH)

AF:

0.00676

AC:

408

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

561

1123

1684

2246

2807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00868

AC:

1322

AN:

152278

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0171

AC:

710

AN:

41560

American (AMR)

AF:

0.00262

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00828

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0124

AC:

131

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00565

AC:

384

AN:

68016

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00547

Hom.:

Bravo

AF:

0.00809

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.0150

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00511

AC:

621

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.034

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.76

PhyloP100

1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

1.0

REVEL

Benign

0.050

Sift

Benign

0.038

Sift4G

Benign

1.0

Polyphen

0.037

Vest4

0.11

MVP

0.17

MPC

0.67

ClinPred

0.0026

GERP RS

2.0

Varity_R

0.063

gMVP

0.31

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over