Variant 13-49482767-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001160308.3(SETDB2):c.1187A>T(p.Lys396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,611,890 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 207 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 190 hom. )

Consequence

SETDB2
NM_001160308.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

SETDB2 links:

SETDB2-PHF11 (HGNC:):

SETDB2-PHF11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018853843).

BP6

Variant 13-49482767-A-T is Benign according to our data. Variant chr13-49482767-A-T is described in ClinVar as [Benign]. Clinvar id is 786240.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETDB2	NM_001160308.3 linkuse as main transcript	c.1187A>T	p.Lys396Ile	missense_variant	9/14	ENST00000611815.2
SETDB2-PHF11	NR_135324.2 linkuse as main transcript	n.2278A>T		non_coding_transcript_exon_variant	10/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETDB2	ENST00000611815.2 linkuse as main transcript	c.1187A>T	p.Lys396Ile	missense_variant	9/14	5	NM_001160308.3	P1	Q96T68-2
SETDB2	ENST00000354234.8 linkuse as main transcript	c.1223A>T	p.Lys408Ile	missense_variant	10/15	1			Q96T68-1
SETDB2	ENST00000317257.12 linkuse as main transcript	c.1187A>T	p.Lys396Ile	missense_variant	8/13	1		P1	Q96T68-2

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4236

AN:

152160

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0978

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00741

AC:

1859

AN:

250714

Hom.:

106

AF XY:

0.00555

AC XY:

753

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00270

AC:

3947

AN:

1459612

Hom.:

190

Cov.:

AF XY:

0.00228

AC XY:

1659

AN XY:

726204

show subpopulations

Gnomad4 AFR exome

AF:

0.0999

Gnomad4 AMR exome

AF:

0.00399

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000774

Gnomad4 OTH exome

AF:

0.00549

GnomAD4 genome

AF:

0.0279

AC:

4253

AN:

152278

Hom.:

207

Cov.:

AF XY:

0.0270

AC XY:

2010

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0979

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.0316

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0996

AC:

439

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00938

AC:

1139

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;.;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.74

T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

M;.;.;.

MutationTaster

Benign

0.85

N;N;N

PrimateAI

Benign

0.34

REVEL

Uncertain

0.38

Sift4G

Benign

0.082

T;D;T;T

Polyphen

0.99

D;.;D;.

Vest4

0.37

MVP

0.84

MPC

1.1

ClinPred

0.030

GERP RS

3.6

Varity_R

0.20

gMVP

0.61

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

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