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GeneBe

9-128683905-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000372692.8(SET):​c.10A>G​(p.Lys4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SET
ENST00000372692.8 missense

Scores

1
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45
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]
HMGA1P4 (HGNC:39093): (high mobility group AT-hook 1 pseudogene 4)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31871715).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SETNM_001122821.2 linkuse as main transcriptc.10A>G p.Lys4Glu missense_variant 1/8
SETNM_001374326.1 linkuse as main transcriptc.10A>G p.Lys4Glu missense_variant 2/9
DYNC2I2XM_011519179.3 linkuse as main transcriptc.-133+461T>C intron_variant
DYNC2I2XM_047424057.1 linkuse as main transcriptc.-133+461T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMGA1P4ENST00000652876.3 linkuse as main transcriptn.128+461T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxOct 04, 2019Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
0.0056
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
0.80
N
PROVEAN
Uncertain
-3.5
D;N
REVEL
Benign
0.18
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.019
D;T
Polyphen
0.96
.;P
Vest4
0.45
MutPred
0.36
Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP
0.58
MPC
2.1
ClinPred
0.99
D
GERP RS
3.9
Varity_R
0.30
gMVP
0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131446184; API