chr14-58270426-TA-CT

Variant names:

• chr14-58270426-TA-CT
• NM_002788.4:c.599_600delTAinsCT
• PSMA3 p.Ile200Thr

Variant summary

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

The NM_002788.4(PSMA3):​c.599_600delTAinsCT​(p.Ile200Thr) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I200V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMA3 NM_002788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.71
• Publications: 0 publications found

Genes affected

PSMA3 (HGNC:9532): (proteasome 20S subunit alpha 3) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 member of the peptidase T1A family, that is a 20S core alpha subunit. Two alternative transcripts encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PSMA3-AS1 (HGNC:26445): (PSMA3 antisense RNA 1)

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002788.4. 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
	PSMA3	NM_002788.4	MANE Select	c.599_600delTAinsCT	p.Ile200Thr	missense	N/A	NP_002779.1	A0A140VK43
	PSMA3	NM_152132.3		c.578_579delTAinsCT	p.Ile193Thr	missense	N/A	NP_687033.1	P25788-2
	PSMA3	NR_038123.2		n.594_595delTAinsCT		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA3	ENST00000216455.9	TSL:1 MANE Select	c.599_600delTAinsCT	p.Ile200Thr	missense	N/A	ENSP00000216455.4	P25788-1
	PSMA3	ENST00000412908.6	TSL:1	c.578_579delTAinsCT	p.Ile193Thr	missense	N/A	ENSP00000390491.2	P25788-2
	PSMA3-AS1	ENST00000554360.5	TSL:1	n.447-3034_447-3033delTAinsAG		intron	N/A

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		6.7

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: chr14-58737144;