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

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

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SET	NM_003011.4	c.132-17C>T		intron_variant	Intron 2 of 7	ENST00000322030.13	NP_003002.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SET	ENST00000322030.13	c.132-17C>T		intron_variant	Intron 2 of 7	1	NM_003011.4	ENSP00000318012.9

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

Gnomad4 AFR exome AF: 0.573 AC: 18825 AN: 32832

Gnomad4 AMR exome AF: 0.966 AC: 40839 AN: 42284

Gnomad4 ASJ exome AF: 0.982 AC: 25300 AN: 25768

Gnomad4 EAS exome AF: 0.884 AC: 34924 AN: 39498

Gnomad4 SAS exome AF: 0.951 AC: 79867 AN: 84022

Gnomad4 FIN exome AF: 0.975 AC: 51683 AN: 52998

Gnomad4 NFE exome AF: 0.997 AC: 1102400 AN: 1105778

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.592 AC: 0.592452 AN: 0.592452

Gnomad4 AMR AF: 0.952 AC: 0.952228 AN: 0.952228

Gnomad4 ASJ AF: 0.981 AC: 0.980991 AN: 0.980991

Gnomad4 EAS AF: 0.901 AC: 0.901118 AN: 0.901118

Gnomad4 SAS AF: 0.939 AC: 0.939388 AN: 0.939388

Gnomad4 FIN AF: 0.970 AC: 0.970011 AN: 0.970011

Gnomad4 NFE AF: 0.996 AC: 0.996208 AN: 0.996208

Gnomad4 OTH AF: 0.903 AC: 0.9035 AN: 0.9035

Alfa AF: 0.947 Hom.: 12726

Bravo AF: 0.858

Asia WGS AF: 0.895 AC: 3113 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual disability, autosomal dominant 58 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.57
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

Publications

LitVar

Other links and lift over

dbSNP: rs3750330; hg19: chr9-131454120;