1-150960992-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001366418.1(SETDB1):c.2933C>T(p.Pro978Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,613,908 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

SETDB1
NM_001366418.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.55

Publications

6 publications found

Variant links:

Genes affected

SETDB1 (HGNC:10761): (SET domain bifurcated histone lysine methyltransferase 1) This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]

SETDB1 links:

CERS2 (HGNC:14076): (ceramide synthase 2) This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

CERS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0079475045).

BP6

Variant 1-150960992-C-T is Benign according to our data. Variant chr1-150960992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETDB1	NM_001366418.1 link	c.2933C>T	p.Pro978Leu	missense_variant	Exon 16 of 22	ENST00000692827.1	NP_001353347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETDB1	ENST00000692827.1 link	c.2933C>T	p.Pro978Leu	missense_variant	Exon 16 of 22		NM_001366418.1	ENSP00000509425.1		A0A8I5KT93

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

362

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00458

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00241

AC:

606

AN:

251464

AF XY:

0.00260

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00323

AC:

4718

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

2408

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00121

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000459

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00545

AC:

470

AN:

86258

European-Finnish (FIN)

AF:

0.00125

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00346

AC:

3845

AN:

1112012

Other (OTH)

AF:

0.00363

AC:

219

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

285

570

854

1139

1424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00237

AC:

360

AN:

152014

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

181

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000507

AC:

AN:

41446

American (AMR)

AF:

0.00223

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00458

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00340

AC:

231

AN:

67970

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00301

Hom.:

Bravo

AF:

0.00260

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00243

AC:

295

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SETDB1: BP4, BS2 -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

-0.067

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.69

N;N;.

PhyloP100

3.6

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.040

D;D;D

Sift4G

Benign

0.32

T;T;T

Polyphen

0.077

B;B;B

Vest4

0.26

MVP

0.61

MPC

0.70

ClinPred

0.014

GERP RS

5.5

Varity_R

0.13

gMVP

0.38

Mutation Taster

=82/18

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.

1-150960992-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over