Variant 1-150929964-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001366418.1(SETDB1):c.261-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00826 in 1,612,404 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0085 ( 80 hom. )

Consequence

SETDB1
NM_001366418.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009894

Clinical Significance

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

Conservation

PhyloP100: 0.348

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 1-150929964-T-C is Benign according to our data. Variant chr1-150929964-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 779065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 903 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETDB1	NM_001366418.1 linkuse as main transcript	c.261-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000692827.1	NP_001353347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETDB1	ENST00000692827.1 linkuse as main transcript	c.261-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001366418.1	ENSP00000509425	A1

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

904

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00571

AC:

1426

AN:

249720

Hom.:

AF XY:

0.00593

AC XY:

801

AN XY:

135016

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00270

Gnomad FIN exome

AF:

0.00389

Gnomad NFE exome

AF:

0.00957

Gnomad OTH exome

AF:

0.00574

GnomAD4 exome

AF:

0.00851

AC:

12421

AN:

1460136

Hom.:

Cov.:

AF XY:

0.00851

AC XY:

6180

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00260

Gnomad4 ASJ exome

AF:

0.00365

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.00455

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00819

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152268

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00786

Hom.:

Bravo

AF:

0.00570

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0108

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	SETDB1: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000099

dbscSNV1_RF

Benign

0.026

SpliceAI score (max)

0.010

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