9-128690006-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003011.4(SET):​c.73+351A>T variant causes a intron 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. 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_003011.4 intron

Scores

1
14

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09971851).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SETNM_003011.4 linkuse as main transcriptc.73+351A>T intron_variant ENST00000322030.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SETENST00000322030.13 linkuse as main transcriptc.73+351A>T intron_variant 1 NM_003011.4 P1Q01105-2

Frequencies

GnomAD3 genomes
AF:
0.0000150
AC:
2
AN:
132918
Hom.:
0
Cov.:
29
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:
4
AN:
899550
Hom.:
0
Cov.:
22
AF XY:
0.00000468
AC XY:
2
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:
2
AN:
132918
Hom.:
0
Cov.:
29
AF XY:
0.0000156
AC XY:
1
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 submitterclinical testingBaylor GeneticsDec 11, 2019This 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
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
18
DANN
Benign
0.93
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.19
T;T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;N;N
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
T
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.

Other links and lift over

dbSNP: rs1190048179; hg19: chr9-131452285; API