12-121902569-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002813.7(PSMD9):c.454-437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 184,438 control chromosomes in the GnomAD database, including 7,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5924 hom., cov: 32)
  • Exomes 𝑓: 0.31 (1654 hom.)
• Consequence: PSMD9 NM_002813.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

PSMD9 (HGNC:9567): (proteasome 26S subunit, non-ATPase 9) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD9	NM_002813.7	c.454-437C>T		intron_variant		ENST00000541212.6
PSMD9	NM_001261400.3	c.139-437C>T		intron_variant
PSMD9	NR_048555.3	n.309-437C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD9	ENST00000541212.6	c.454-437C>T		intron_variant		1	NM_002813.7	P4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37837 AN: 151962 Hom.: 5918 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.311 AC: 10070 AN: 32358 Hom.: 1654 Cov.: 0 AF XY: 0.308 AC XY: 5260 AN XY: 17104

Gnomad4 AFR exome AF: 0.0541

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.249 AC: 37850 AN: 152080 Hom.: 5924 Cov.: 32 AF XY: 0.255 AC XY: 18916 AN XY: 74298

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.273

Alfa AF: 0.173 Hom.: 401

Bravo AF: 0.242

Asia WGS AF: 0.402 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.93
Dann	Benign	0.79

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: rs3825172; hg19: chr12-122340475;