9-128683961-G-T

Variant names:

• chr9-128683961-G-T
• rs191311210
• ENST00000372692.8:c.66G>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001122821.2(SET):​c.66G>T​(p.Leu22Leu) 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 NM_001122821.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399

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]

DYNC2I2 (HGNC:28296): (dynein 2 intermediate chain 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Defects in this gene are a cause of short-rib thoracic dysplasia 11 with or without polydactyly. [provided by RefSeq, Mar 2014]

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

ACMG classification

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 rank	MANE	Protein	UniProt
SET	NM_001122821.2	c.66G>T	p.Leu22Leu	synonymous_variant	Exon 1 of 8		NP_001116293.1
SET	NM_001374326.1	c.66G>T	p.Leu22Leu	synonymous_variant	Exon 2 of 9		NP_001361255.1
DYNC2I2	XM_047424057.1	c.-133+405C>A		intron_variant	Intron 1 of 9		XP_047280013.1
DYNC2I2	XM_011519179.3	c.-133+405C>A		intron_variant	Intron 1 of 9		XP_011517481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SET	ENST00000372692.8	c.66G>T	p.Leu22Leu	synonymous_variant	Exon 1 of 8	1		ENSP00000361777.4
SET	ENST00000686840.1	c.66G>T	p.Leu22Leu	synonymous_variant	Exon 2 of 9			ENSP00000509032.1
SET	ENST00000686568.1	c.66G>T	p.Leu22Leu	synonymous_variant	Exon 1 of 7			ENSP00000508597.1

Frequencies

GnomAD3 genomes AF: 0.00595 AC: 905 AN: 152134 Hom.: 8 Cov.: 31

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.: 3 AF XY: 0.00261 AC XY: 227 AN XY: 86836

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.: 10 Cov.: 30 AF XY: 0.00177 AC XY: 1228 AN XY: 693576

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.: 8 Cov.: 31 AF XY: 0.00576 AC XY: 429 AN XY: 74438

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.: 0

Bravo AF: 0.00694

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs191311210; hg19: chr9-131446240;