dbSNP rs37036: SETD6:n.*1007T>C (chr16-58519444-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000427443.5(SETD6):n.*1007T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 175,144 control chromosomes in the GnomAD database, including 5,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5046 hom., cov: 32)

Exomes 𝑓: 0.27 ( 937 hom. )

Consequence

SETD6
ENST00000427443.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

18 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SETD6	NM_001160305.4 link	c.*415T>C	3_prime_UTR_variant	Exon 8 of 8	ENST00000219315.9	NP_001153777.1	Q8TBK2-1
SETD6	NR_134583.1 link	n.1855T>C	non_coding_transcript_exon_variant	Exon 9 of 9
SETD6	NM_024860.3 link	c.*415T>C	3_prime_UTR_variant	Exon 9 of 9		NP_079136.2	Q8TBK2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD6	ENST00000219315.9 link	c.*415T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001160305.4	ENSP00000219315.5		Q8TBK2-1

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37480

AN:

151950

Hom.:

5031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.267

AC:

6162

AN:

23076

Hom.:

937

Cov.:

AF XY:

0.272

AC XY:

3329

AN XY:

12252

show subpopulations

African (AFR)

AF:

0.143

AC:

AN:

462

American (AMR)

AF:

0.399

AC:

1309

AN:

3280

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

AN:

428

East Asian (EAS)

AF:

0.367

AC:

531

AN:

1446

South Asian (SAS)

AF:

0.289

AC:

902

AN:

3124

European-Finnish (FIN)

AF:

0.215

AC:

109

AN:

508

Middle Eastern (MID)

AF:

0.0750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.226

AC:

2896

AN:

12788

Other (OTH)

AF:

0.251

AC:

251

AN:

1000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

210

421

631

842

1052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.247

AC:

37521

AN:

152068

Hom.:

5046

Cov.:

AF XY:

0.252

AC XY:

18763

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.158

AC:

6570

AN:

41478

American (AMR)

AF:

0.350

AC:

5351

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

907

AN:

3470

East Asian (EAS)

AF:

0.381

AC:

1965

AN:

5164

South Asian (SAS)

AF:

0.337

AC:

1625

AN:

4820

European-Finnish (FIN)

AF:

0.292

AC:

3089

AN:

10566

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17251

AN:

67978

Other (OTH)

AF:

0.238

AC:

503

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1432

2863

4295

5726

7158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.249

Hom.:

7820

Bravo

AF:

0.247

Asia WGS

AF:

0.353

AC:

1229

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.51

(source)

DANN

Benign

0.45

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over