Genetic Variant SETD6:p.Pro142Arg (chr16-58516292-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001160305.4(SETD6):c.425C>G(p.Pro142Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00019 in 1,605,092 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

SETD6
NM_001160305.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

Publications

1 publications found

Variant links:

Genes affected

SETD6 (HGNC:26116): (SET domain containing 6, protein lysine methyltransferase) This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SETD6 Gene-Disease associations (from GenCC):

colorectal cancer
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

SETD6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03449726).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160305.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD6	NM_001160305.4	MANE Select	c.425C>G	p.Pro142Arg	missense	Exon 3 of 8	NP_001153777.1	Q8TBK2-1
SETD6	NM_024860.3		c.353C>G	p.Pro118Arg	missense	Exon 4 of 9	NP_079136.2	Q8TBK2-2
SETD6	NR_134583.1		n.412C>G		non_coding_transcript_exon	Exon 4 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD6	ENST00000219315.9	TSL:1 MANE Select	c.425C>G	p.Pro142Arg	missense	Exon 3 of 8	ENSP00000219315.5	Q8TBK2-1
SETD6	ENST00000427443.5	TSL:1	n.353C>G		non_coding_transcript_exon	Exon 4 of 9	ENSP00000398033.1	E9PC53
SETD6	ENST00000310682.6	TSL:2	c.353C>G	p.Pro118Arg	missense	Exon 4 of 9	ENSP00000310082.2	Q8TBK2-2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000297

AC:

AN:

239020

AF XY:

0.000304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.000180

AC:

262

AN:

1452840

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

158

AN XY:

723190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.0000672

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000220

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.000156

AC:

AN:

44898

Middle Eastern (MID)

AF:

0.00125

AC:

AN:

5592

European-Non Finnish (NFE)

AF:

0.000140

AC:

156

AN:

1111882

Other (OTH)

AF:

0.000299

AC:

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.000282

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000427

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000560

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000476

AC:

ExAC

AF:

0.000273

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.25

M_CAP

Benign

0.023

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.98

PhyloP100

3.8

PROVEAN

Benign

0.75

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.70

MVP

0.37

ClinPred

0.36

GERP RS

3.2

Varity_R

0.58

Mutation Taster

=36/64

disease causing

(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