Variant 1-150949193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001366418.1(SETDB1):c.1339C>T(p.Pro447Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

SETDB1
NM_001366418.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, SETDB1

BP4

Computational evidence support a benign effect (MetaRNN=0.005208373).

BP6

Variant 1-150949193-C-T is Benign according to our data. Variant chr1-150949193-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 725264.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETDB1	NM_001366418.1 linkuse as main transcript	c.1339C>T	p.Pro447Ser	missense_variant	11/22	ENST00000692827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETDB1	ENST00000692827.1 linkuse as main transcript	c.1339C>T	p.Pro447Ser	missense_variant	11/22		NM_001366418.1	A1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000479

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251438

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000499

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000394

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.000574

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.060

T;T;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.4

L;.;L;.

MutationTaster

Benign

0.96

D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.24

N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.56

T;D;T;T

Polyphen

0.0040

B;B;B;B

Vest4

0.18

MVP

0.51

MPC

0.62

ClinPred

0.024

GERP RS

4.4

Varity_R

0.054

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over