Genetic Variant SETD6:p.Gly107Asp (chr16-58516083-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001160305.4(SETD6):c.320G>A(p.Gly107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,416,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SETD6
NM_001160305.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0580

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020309806).

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.320G>A	p.Gly107Asp	missense	Exon 2 of 8	NP_001153777.1	Q8TBK2-1
SETD6	NM_024860.3		c.248G>A	p.Gly83Asp	missense	Exon 3 of 9	NP_079136.2	Q8TBK2-2
SETD6	NR_134583.1		n.307G>A		non_coding_transcript_exon	Exon 3 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD6	ENST00000219315.9	TSL:1 MANE Select	c.320G>A	p.Gly107Asp	missense	Exon 2 of 8	ENSP00000219315.5	Q8TBK2-1
SETD6	ENST00000427443.5	TSL:1	n.248G>A		non_coding_transcript_exon	Exon 3 of 9	ENSP00000398033.1	E9PC53
SETD6	ENST00000310682.6	TSL:2	c.248G>A	p.Gly83Asp	missense	Exon 3 of 9	ENSP00000310082.2	Q8TBK2-2

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

148784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000399

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000395

AC:

AN:

50682

AF XY:

0.0000687

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000485

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1267814

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

621420

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26252

American (AMR)

AF:

0.00

AC:

AN:

20596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19916

East Asian (EAS)

AF:

0.00

AC:

AN:

28286

South Asian (SAS)

AF:

0.0000487

AC:

AN:

61552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3868

European-Non Finnish (NFE)

AF:

0.00000489

AC:

AN:

1023372

Other (OTH)

AF:

0.000287

AC:

AN:

52334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000269

AC:

AN:

148894

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

72600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40738

American (AMR)

AF:

0.00

AC:

AN:

14960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.000400

AC:

AN:

5002

South Asian (SAS)

AF:

0.00

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67028

Other (OTH)

AF:

0.000968

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000202

AC:

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

Benign

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0063

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.55

M_CAP

Benign

0.018

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.93

PhyloP100

0.058

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.64

REVEL

Benign

0.033

Sift

Benign

0.78

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.087

MutPred

0.35

Loss of helix (P = 0.0558)

MVP

0.19

MPC

0.25

ClinPred

0.042

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.34

Mutation Taster

=84/16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over