Variant 21-36036228-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017438.5(SETD4):c.1212A>T(p.Lys404Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,609,066 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 17 hom. )

Consequence

SETD4
NM_017438.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.16

Variant links:

Genes affected

SETD4 (HGNC:1258): (SET domain containing 4) Enables histone methyltransferase activity (H4-K20 specific). Involved in histone H4-K20 trimethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SETD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030344427).

BP6

Variant 21-36036228-T-A is Benign according to our data. Variant chr21-36036228-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652639.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD4	NM_017438.5 linkuse as main transcript	c.1212A>T	p.Lys404Asn	missense_variant	11/12	ENST00000332131.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD4	ENST00000332131.9 linkuse as main transcript	c.1212A>T	p.Lys404Asn	missense_variant	11/12	2	NM_017438.5	P1	Q9NVD3-1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00453

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00296

AC:

726

AN:

244864

Hom.:

AF XY:

0.00315

AC XY:

416

AN XY:

132134

show subpopulations

Gnomad AFR exome

AF:

0.000743

Gnomad AMR exome

AF:

0.00403

Gnomad ASJ exome

AF:

0.000515

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.00475

Gnomad OTH exome

AF:

0.00470

GnomAD4 exome

AF:

0.00394

AC:

5733

AN:

1456734

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

2776

AN XY:

724350

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.000424

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000401

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00469

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.00270

AC:

411

AN:

152332

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

191

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00409

Hom.:

Bravo

AF:

0.00324

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00274

AC:

333

EpiCase

AF:

0.00556

EpiControl

AF:

0.00611

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

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

SETD4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

Cadd

Benign

0.23

Dann

Benign

0.80

DEOGEN2

Benign

0.0096

T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.083

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.35

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.45

T;.;T

Polyphen

0.0010

B;B;B

Vest4

0.053

MutPred

0.41

Loss of ubiquitination at K404 (P = 0.0047);.;Loss of ubiquitination at K404 (P = 0.0047);

MVP

0.17

MPC

0.22

ClinPred

0.0065

GERP RS

-0.90

Varity_R

0.036

gMVP

0.12

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