9-128691841-C-T

Variant names:

• chr9-128691841-C-T
• rs3750330
• NM_003011.4:c.132-17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003011.4(SET):​c.132-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 1,600,674 control chromosomes in the GnomAD database, including 756,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (60365 hom., cov: 33)
  • Exomes 𝑓: 0.98 (695969 hom.)
• Consequence: SET NM_003011.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.361
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 58

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000305868 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-128691841-C-T is Benign according to our data. Variant chr9-128691841-C-T is described in ClinVar as Benign. ClinVar VariationId is 1332943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SET	NM_003011.4	MANE Select	c.132-17C>T		intron	N/A	NP_003002.2	Q01105-2
	SET	NM_001122821.2		c.171-17C>T		intron	N/A	NP_001116293.1	Q5VXV3
	SET	NM_001374326.1		c.171-17C>T		intron	N/A	NP_001361255.1	Q5VXV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SET	ENST00000322030.13	TSL:1 MANE Select	c.132-17C>T		intron	N/A	ENSP00000318012.9	Q01105-2
	SET	ENST00000372692.8	TSL:1	c.171-17C>T		intron	N/A	ENSP00000361777.4	Q01105-1
	SET	ENST00000477806.5	TSL:1	n.323-17C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132877 AN: 152110 Hom.: 60342 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.904

GnomAD2 exomes AF: 0.950 AC: 225226 AN: 236980 AF XY: 0.957

Gnomad AFR exome AF: 0.581

Gnomad AMR exome AF: 0.968

Gnomad ASJ exome AF: 0.980

Gnomad EAS exome AF: 0.906

Gnomad FIN exome AF: 0.974

Gnomad NFE exome AF: 0.995

Gnomad OTH exome AF: 0.968

GnomAD4 exome AF: 0.978 AC: 1416538 AN: 1448446 Hom.: 695969 Cov.: 30 AF XY: 0.979 AC XY: 704631 AN XY: 720022

African (AFR) AF: 0.573 AC: 18825 AN: 32832

American (AMR) AF: 0.966 AC: 40839 AN: 42284

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 25300 AN: 25768

East Asian (EAS) AF: 0.884 AC: 34924 AN: 39498

South Asian (SAS) AF: 0.951 AC: 79867 AN: 84022

European-Finnish (FIN) AF: 0.975 AC: 51683 AN: 52998

Middle Eastern (MID) AF: 0.974 AC: 5338 AN: 5482

European-Non Finnish (NFE) AF: 0.997 AC: 1102400 AN: 1105778

Other (OTH) AF: 0.959 AC: 57362 AN: 59784

GnomAD4 genome AF: 0.873 AC: 132938 AN: 152228 Hom.: 60365 Cov.: 33 AF XY: 0.873 AC XY: 65024 AN XY: 74450

African (AFR) AF: 0.592 AC: 24569 AN: 41470

American (AMR) AF: 0.952 AC: 14571 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 3406 AN: 3472

East Asian (EAS) AF: 0.901 AC: 4675 AN: 5188

South Asian (SAS) AF: 0.939 AC: 4541 AN: 4834

European-Finnish (FIN) AF: 0.970 AC: 10286 AN: 10604

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67780 AN: 68038

Other (OTH) AF: 0.903 AC: 1910 AN: 2114

Alfa AF: 0.947 Hom.: 12726

Bravo AF: 0.858

Asia WGS AF: 0.895 AC: 3113 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, autosomal dominant 58 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.57
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3750330; hg19: chr9-131454120;