Variant 9-128683960-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000372692.8(SET):c.65T>C(p.Leu22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,557,540 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L22L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

SET
ENST00000372692.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0550

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003423959).

BP6

Variant 9-128683960-T-C is Benign according to our data. Variant chr9-128683960-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3025809.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 362 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
SET	NM_001122821.2 linkuse as main transcript	c.65T>C	p.Leu22Pro	missense_variant	1/8
SET	NM_001374326.1 linkuse as main transcript	c.65T>C	p.Leu22Pro	missense_variant	2/9
DYNC2I2	XM_011519179.3 linkuse as main transcript	c.-133+406A>G		intron_variant
DYNC2I2	XM_047424057.1 linkuse as main transcript	c.-133+406A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA1P4	ENST00000652876.3 linkuse as main transcript	n.128+406A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

362

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00840

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000556

AC:

AN:

163656

Hom.:

AF XY:

0.000505

AC XY:

AN XY:

87052

show subpopulations

Gnomad AFR exome

AF:

0.00908

Gnomad AMR exome

AF:

0.000158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000155

Gnomad OTH exome

AF:

0.000217

GnomAD4 exome

AF:

0.000235

AC:

330

AN:

1405282

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

147

AN XY:

693684

show subpopulations

Gnomad4 AFR exome

AF:

0.00908

Gnomad4 AMR exome

AF:

0.000110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000176

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000277

Gnomad4 OTH exome

AF:

0.000343

GnomAD4 genome

AF:

0.00238

AC:

362

AN:

152258

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00838

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00246

ESP6500AA

AF:

0.00837

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000508

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

SET: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.3

DANN

Benign

0.36

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

.;N

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-4.7

D;N

REVEL

Benign

0.025

Sift

Uncertain

0.014

D;T

Sift4G

Benign

0.089

T;T

Polyphen

0.0030

.;B

Vest4

0.084

MVP

0.068

MPC

2.6

ClinPred

0.025

GERP RS

1.3

Varity_R

0.080

gMVP

0.32

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