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9-128683961-G-T

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Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000372692.8(SET):​c.66G>T​(p.Leu22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,557,270 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 31)
Exomes 𝑓: 0.0018 ( 10 hom. )

Consequence

SET
ENST00000372692.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.399
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 Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-128683961-G-T is Benign according to our data. Variant chr9-128683961-G-T is described in ClinVar as [Benign]. Clinvar id is 774204.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.399 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00182 (2563/1405018) while in subpopulation AFR AF= 0.018 (573/31820). AF 95% confidence interval is 0.0168. There are 10 homozygotes in gnomad4_exome. There are 1228 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd4 at 902 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SETNM_001122821.2 linkuse as main transcriptc.66G>T p.Leu22= synonymous_variant 1/8
SETNM_001374326.1 linkuse as main transcriptc.66G>T p.Leu22= synonymous_variant 2/9
DYNC2I2XM_011519179.3 linkuse as main transcriptc.-133+405C>A intron_variant
DYNC2I2XM_047424057.1 linkuse as main transcriptc.-133+405C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMGA1P4ENST00000652876.3 linkuse as main transcriptn.128+405C>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00595
AC:
905
AN:
152134
Hom.:
8
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0155
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00675
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00159
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00296
AC:
483
AN:
163212
Hom.:
3
AF XY:
0.00261
AC XY:
227
AN XY:
86836
show subpopulations
Gnomad AFR exome
AF:
0.0164
Gnomad AMR exome
AF:
0.00561
Gnomad ASJ exome
AF:
0.00546
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000868
Gnomad FIN exome
AF:
0.000174
Gnomad NFE exome
AF:
0.00173
Gnomad OTH exome
AF:
0.00740
GnomAD4 exome
AF:
0.00182
AC:
2563
AN:
1405018
Hom.:
10
Cov.:
30
AF XY:
0.00177
AC XY:
1228
AN XY:
693576
show subpopulations
Gnomad4 AFR exome
AF:
0.0180
Gnomad4 AMR exome
AF:
0.00580
Gnomad4 ASJ exome
AF:
0.00575
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000201
Gnomad4 FIN exome
AF:
0.000221
Gnomad4 NFE exome
AF:
0.00121
Gnomad4 OTH exome
AF:
0.00435
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00592
AC:
902
AN:
152252
Hom.:
8
Cov.:
31
AF XY:
0.00576
AC XY:
429
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0154
Gnomad4 AMR
AF:
0.00674
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00159
Gnomad4 OTH
AF:
0.0113
Alfa
AF:
0.00290
Hom.:
0
Bravo
AF:
0.00694
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.89
DANN
Benign
0.56

Splicing

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: rs191311210; hg19: chr9-131446240; API