9-128690034-C-T

Position:

• chr9-128690034-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003011.4(SET):​c.73+379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,024,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00082 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: SET NM_003011.4 intron
• Scores: Splicing: ADA: 0.0001700
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.152

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 9-128690034-C-T is Benign according to our data. Variant chr9-128690034-C-T is described in ClinVar as [Benign]. Clinvar id is 1711695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SET	NM_003011.4	c.73+379C>T		intron_variant		ENST00000322030.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SET	ENST00000322030.13	c.73+379C>T		intron_variant		1	NM_003011.4	P1

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 120 AN: 146114 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000406

Gnomad ASJ AF: 0.00236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.00150

GnomAD3 exomes AF: 0.00110 AC: 29 AN: 26270 Hom.: 0 AF XY: 0.00124 AC XY: 20 AN XY: 16146

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00455

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00116 AC: 1017 AN: 878006 Hom.: 1 Cov.: 18 AF XY: 0.00125 AC XY: 518 AN XY: 415416

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00393

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.000986

GnomAD4 genome AF: 0.000821 AC: 120 AN: 146114 Hom.: 0 Cov.: 30 AF XY: 0.000703 AC XY: 50 AN XY: 71090

Gnomad4 AFR AF: 0.000123

Gnomad4 AMR AF: 0.000406

Gnomad4 ASJ AF: 0.00236

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00145

Gnomad4 OTH AF: 0.00150

Alfa AF: 0.000838 Hom.: 0

Bravo AF: 0.000793

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

SET: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs750117490; hg19: chr9-131452313;