Variant chr9-128690006-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM1PP2BP4_Moderate

The NM_001248001.2(SET):c.20A>T(p.Gln7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000581 in 1,032,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

SET
NM_001248001.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

Variant links:

Genes affected

SET (HGNC:10760): (SET nuclear proto-oncogene) The protein encoded by this gene inhibits acetylation of nucleosomes, especially histone H4, by histone acetylases (HAT). This inhibition is most likely accomplished by masking histone lysines from being acetylated, and the consequence is to silence HAT-dependent transcription. The encoded protein is part of a complex localized to the endoplasmic reticulum but is found in the nucleus and inhibits apoptosis following attack by cytotoxic T lymphocytes. This protein can also enhance DNA replication of the adenovirus genome. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SET links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity SET_HUMAN

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SET. . Gene score misZ 2.6574 (greater than the threshold 3.09). Trascript score misZ 3.2041 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant non-syndromic intellectual disability, intellectual disability, autosomal dominant 58.

BP4

Computational evidence support a benign effect (MetaRNN=0.09971851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SET	NM_003011.4 linkuse as main transcript	c.73+351A>T		intron_variant		ENST00000322030.13	NP_003002.2	Q01105-2A0A024R895

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SET	ENST00000322030.13 linkuse as main transcript	c.73+351A>T		intron_variant		1	NM_003011.4	ENSP00000318012.9		Q01105-2

Frequencies

GnomAD3 genomes

AF:

0.0000150

AC:

AN:

132918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000320

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000445

AC:

AN:

899550

Hom.:

Cov.:

AF XY:

0.00000468

AC XY:

AN XY:

427602

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000503

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000150

AC:

AN:

132918

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

63942

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000320

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 58

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Dec 11, 2019

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.19

T;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.86

N;N

REVEL

Benign

0.0030

Sift

Benign

0.090

T;T

Sift4G

Benign

0.27

T;T

Vest4

0.16

MutPred

0.30

Gain of catalytic residue at Q7 (P = 0.0098);.;

MVP

0.38

ClinPred

0.11

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

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