Genetic Variant SETD6:p.Glu161Gln (chr16-58516482-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001160305.4(SETD6):c.481G>C(p.Glu161Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,716 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. 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. E161K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SETD6
NM_001160305.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.00

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18303075).

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.481G>C	p.Glu161Gln	missense	Exon 4 of 8	NP_001153777.1	Q8TBK2-1
SETD6	NM_024860.3		c.409G>C	p.Glu137Gln	missense	Exon 5 of 9	NP_079136.2	Q8TBK2-2
SETD6	NR_134583.1		n.468G>C		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD6	ENST00000219315.9	TSL:1 MANE Select	c.481G>C	p.Glu161Gln	missense	Exon 4 of 8	ENSP00000219315.5	Q8TBK2-1
SETD6	ENST00000427443.5	TSL:1	n.409G>C		non_coding_transcript_exon	Exon 5 of 9	ENSP00000398033.1	E9PC53
SETD6	ENST00000310682.6	TSL:2	c.409G>C	p.Glu137Gln	missense	Exon 5 of 9	ENSP00000310082.2	Q8TBK2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111942

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.026

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

M_CAP

Benign

0.0083

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

3.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

REVEL

Benign

0.084

Sift

Benign

0.080

Sift4G

Benign

0.17

Polyphen

0.032

Vest4

0.29

MutPred

0.63

Loss of glycosylation at P160 (P = 0.0766)

MVP

0.44

MPC

0.35

ClinPred

0.68

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.28

gMVP

0.41

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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