Variant chr9-128683961-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

SET links:

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

HMGA1P4 links:

DYNC2I2 (HGNC:):

DYNC2I2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.399 with no splicing effect.

BS1

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

High AC in GnomAd4 at 902 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
SET	NM_001122821.2 linkuse as main transcript	c.66G>T	p.Leu22=	synonymous_variant	1/8
SET	NM_001374326.1 linkuse as main transcript	c.66G>T	p.Leu22=	synonymous_variant	2/9
DYNC2I2	XM_011519179.3 linkuse as main transcript	c.-133+405C>A		intron_variant
DYNC2I2	XM_047424057.1 linkuse as main transcript	c.-133+405C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA1P4	ENST00000652876.3 linkuse as main transcript	n.128+405C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00595

AC:

905

AN:

152134

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00592

AC:

902

AN:

152252

Hom.:

Cov.:

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.:

Bravo

AF:

0.00694

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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.

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