chr12-121902546-G-A

Position:

• chr12-121902546-G-A

Variant summary

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

The NM_002813.7(PSMD9):​c.454-460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 166,040 control chromosomes in the GnomAD database, including 6,649 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 (725 hom.)
• Consequence: PSMD9 NM_002813.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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=-0.85).
• 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	Protein	UniProt
PSMD9	NM_002813.7	c.454-460G>A		intron_variant		ENST00000541212.6	NP_002804.2
PSMD9	NM_001261400.3	c.139-460G>A		intron_variant			NP_001248329.1
PSMD9	NR_048555.3	n.309-460G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD9	ENST00000541212.6	c.454-460G>A		intron_variant		1	NM_002813.7	ENSP00000440485	P4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37906 AN: 152004 Hom.: 5918 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.314 AC: 4374 AN: 13918 Hom.: 725 Cov.: 0 AF XY: 0.310 AC XY: 2276 AN XY: 7352

Gnomad4 AFR exome AF: 0.0532

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.249 AC: 37919 AN: 152122 Hom.: 5924 Cov.: 32 AF XY: 0.255 AC XY: 18954 AN XY: 74336

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.274

Alfa AF: 0.296 Hom.: 1340

Bravo AF: 0.243

Asia WGS AF: 0.405 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.64

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: rs74421874; hg19: chr12-122340452;