Genetic Variant NM_005977.4:c.1089A>G (chr13-26214793-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005977.4(RNF6):c.1089A>G(p.Ala363Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RNF6
NM_005977.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.400

Publications

1 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-26214793-T-C is Benign according to our data. Variant chr13-26214793-T-C is described in ClinVar as Benign. ClinVar VariationId is 730413.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.4 with no splicing effect.

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.1089A>G	p.Ala363Ala	synonymous	Exon 5 of 5	NP_005968.1	A0A024RDP2
RNF6	NM_183043.3		c.1089A>G	p.Ala363Ala	synonymous	Exon 5 of 5	NP_898864.1	Q9Y252-1
RNF6	NM_183044.3		c.1089A>G	p.Ala363Ala	synonymous	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.1089A>G	p.Ala363Ala	synonymous	Exon 5 of 5	ENSP00000371000.4	Q9Y252-1
RNF6	ENST00000346166.7	TSL:1	c.1089A>G	p.Ala363Ala	synonymous	Exon 5 of 5	ENSP00000342121.3	Q9Y252-1
RNF6	ENST00000381570.7	TSL:1	c.1089A>G	p.Ala363Ala	synonymous	Exon 5 of 5	ENSP00000370982.3	Q9Y252-1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000294

AC:

AN:

251428

AF XY:

0.000199

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000147

AC:

215

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00400

AC:

134

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1112000

Other (OTH)

AF:

0.000348

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00119

AC:

182

AN:

152336

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00428

AC:

178

AN:

41572

American (AMR)

AF:

0.000196

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000638

Hom.:

Bravo

AF:

0.00133

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.6

(source)

DANN

Benign

0.48

PhyloP100

-0.40

La Branchor

0.89

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