12-121915890-AA-GT

Variant names:

• chr12-121915890-AA-GT
• NM_002813.7:c.590_591delAAinsGT
• PSMD9 p.Glu197Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002813.7(PSMD9):​c.590_591delAAinsGT​(p.Glu197Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E197V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMD9 NM_002813.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002813.7. 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
	PSMD9	NM_002813.7	MANE Select	c.590_591delAAinsGT	p.Glu197Gly	missense	N/A	NP_002804.2
	PSMD9	NM_001261400.3		c.275_276delAAinsGT	p.Glu92Gly	missense	N/A	NP_001248329.1	O00233-3
	PSMD9	NR_048555.3		n.445_446delAAinsGT		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD9	ENST00000541212.6	TSL:1 MANE Select	c.590_591delAAinsGT	p.Glu197Gly	missense	N/A	ENSP00000440485.1	O00233-1
	PSMD9	ENST00000537407.5	TSL:1	n.*25_*26delAAinsGT		non_coding_transcript_exon	Exon 6 of 7	ENSP00000445058.1	O00233-2
	PSMD9	ENST00000537407.5	TSL:1	n.*25_*26delAAinsGT		3_prime_UTR	Exon 6 of 7	ENSP00000445058.1	O00233-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-122353796;