12-121905058-T-C

Variant names:

• chr12-121905058-T-C
• rs7314056
• NM_002813.7:c.555+1951T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002813.7(PSMD9):​c.555+1951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 151,660 control chromosomes in the GnomAD database, including 58,909 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 0.88 (58909 hom., cov: 30)
• Consequence: PSMD9 NM_002813.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 17 publications found

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]

ENSG00000256950 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD9	NM_002813.7	c.555+1951T>C		intron_variant	Intron 4 of 5	ENST00000541212.6	NP_002804.2
PSMD9	NM_001261400.3	c.240+1951T>C		intron_variant	Intron 2 of 3		NP_001248329.1
PSMD9	NR_048555.3	n.410+1951T>C		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD9	ENST00000541212.6	c.555+1951T>C		intron_variant	Intron 4 of 5	1	NM_002813.7	ENSP00000440485.1
ENSG00000256950	ENST00000546333.1	n.*85+1951T>C		intron_variant	Intron 3 of 3	5		ENSP00000477146.1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133225 AN: 151544 Hom.: 58858 Cov.: 30

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.873

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.879 AC: 133331 AN: 151660 Hom.: 58909 Cov.: 30 AF XY: 0.873 AC XY: 64733 AN XY: 74120

African (AFR) AF: 0.958 AC: 39376 AN: 41090

American (AMR) AF: 0.795 AC: 12127 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3156 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4461 AN: 5158

South Asian (SAS) AF: 0.844 AC: 4075 AN: 4826

European-Finnish (FIN) AF: 0.771 AC: 8139 AN: 10558

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59051 AN: 68000

Other (OTH) AF: 0.875 AC: 1849 AN: 2112

Alfa AF: 0.867 Hom.: 94436

Bravo AF: 0.885

Asia WGS AF: 0.870 AC: 3022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.80
PhyloP100		-0.72
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

Other links and lift over

dbSNP: rs7314056; hg19: chr12-122342964;