dbSNP rs552852112: SETD6:p.Glu81Gln (chr16-58516004-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001160305.4(SETD6):c.241G>C(p.Glu81Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000712 in 1,543,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SETD6
NM_001160305.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90

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: Uncertain_significance. The variant received 0 ACMG points.

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.241G>C	p.Glu81Gln	missense	Exon 2 of 8	NP_001153777.1	Q8TBK2-1
SETD6	NM_024860.3		c.169G>C	p.Glu57Gln	missense	Exon 3 of 9	NP_079136.2	Q8TBK2-2
SETD6	NR_134583.1		n.228G>C		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.241G>C	p.Glu81Gln	missense	Exon 2 of 8	ENSP00000219315.5	Q8TBK2-1
SETD6	ENST00000427443.5	TSL:1	n.169G>C		non_coding_transcript_exon	Exon 3 of 9	ENSP00000398033.1	E9PC53
SETD6	ENST00000310682.6	TSL:2	c.169G>C	p.Glu57Gln	missense	Exon 3 of 9	ENSP00000310082.2	Q8TBK2-2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

147524

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1391738

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689686

show subpopulations

African (AFR)

AF:

0.0000684

AC:

AN:

29260

American (AMR)

AF:

0.00

AC:

AN:

36798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24518

East Asian (EAS)

AF:

0.00

AC:

AN:

34098

South Asian (SAS)

AF:

0.00

AC:

AN:

78974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088100

Other (OTH)

AF:

0.00

AC:

AN:

58040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000591

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

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:

0.00

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.00000879

AC:

ClinVar

ClinVar submissions as Germline

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

0.11

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.91

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

1.4

PhyloP100

6.9

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.41

Sift

Benign

0.071

Sift4G

Uncertain

0.023

Polyphen

0.77

Vest4

0.26

MutPred

0.73

Gain of MoRF binding (P = 0.0269)

MVP

0.66

MPC

0.31

ClinPred

0.96

GERP RS

5.3

PromoterAI

-0.0022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.46

gMVP

0.46

Mutation Taster

=45/55

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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