chr9-128683961-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

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

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 1228 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 902 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122821.2. 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_001122821.2		c.66G>T	p.Leu22Leu	synonymous	Exon 1 of 8	NP_001116293.1	Q5VXV3
	SET	NM_001374326.1		c.66G>T	p.Leu22Leu	synonymous	Exon 2 of 9	NP_001361255.1	Q5VXV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SET	ENST00000372692.8	TSL:1	c.66G>T	p.Leu22Leu	synonymous	Exon 1 of 8	ENSP00000361777.4	Q01105-1
	SET	ENST00000921998.1		c.-51G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000592057.1
	SET	ENST00000686840.1		c.66G>T	p.Leu22Leu	synonymous	Exon 2 of 9	ENSP00000509032.1	Q01105-1

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

GnomAD2 exomes AF: 0.00296 AC: 483 AN: 163212 AF XY: 0.00261

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 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

African (AFR) AF: 0.0180 AC: 573 AN: 31820

American (AMR) AF: 0.00580 AC: 210 AN: 36230

Ashkenazi Jewish (ASJ) AF: 0.00575 AC: 145 AN: 25228

East Asian (EAS) AF: 0.00 AC: 0 AN: 36064

South Asian (SAS) AF: 0.000201 AC: 16 AN: 79432

European-Finnish (FIN) AF: 0.000221 AC: 11 AN: 49800

Middle Eastern (MID) AF: 0.00859 AC: 49 AN: 5702

European-Non Finnish (NFE) AF: 0.00121 AC: 1305 AN: 1082408

Other (OTH) AF: 0.00435 AC: 254 AN: 58334

GnomAD4 genome AF: 0.00592 AC: 902 AN: 152252 Hom.: 8 Cov.: 31 AF XY: 0.00576 AC XY: 429 AN XY: 74438

African (AFR) AF: 0.0154 AC: 641 AN: 41550

American (AMR) AF: 0.00674 AC: 103 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00159 AC: 108 AN: 68008

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.00290 Hom.: 0

Bravo AF: 0.00694

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.89
DANN	Benign	0.56
PhyloP100		-0.40
PromoterAI		-0.087	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs191311210; hg19: chr9-131446240;