15-78545747-ATT-GTA

Variant names:

• chr15-78545747-ATT-GTA
• NM_002789.6:c.490_492delATTinsGTA
• PSMA4 p.Ile164Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002789.6(PSMA4):​c.490_492delATTinsGTA​(p.Ile164Val) variant causes a missense change involving the alteration of a 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMA4 NM_002789.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.06
• Publications: 0 publications found

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002789.6. 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
	PSMA4	NM_002789.6	MANE Select	c.490_492delATTinsGTA	p.Ile164Val	missense	N/A	NP_002780.1	P25789-1
	PSMA4	NM_001102667.2		c.490_492delATTinsGTA	p.Ile164Val	missense	N/A	NP_001096137.1	P25789-1
	PSMA4	NM_001330676.2		c.490_492delATTinsGTA	p.Ile164Val	missense	N/A	NP_001317605.1	P25789-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	ENST00000044462.12	TSL:1 MANE Select	c.490_492delATTinsGTA	p.Ile164Val	missense	N/A	ENSP00000044462.7	P25789-1
	PSMA4	ENST00000413382.6	TSL:1	c.277_279delATTinsGTA	p.Ile93Val	missense	N/A	ENSP00000402118.2	P25789-2
	PSMA4	ENST00000559934.5	TSL:1	n.2483_2485delATTinsGTA		non_coding_transcript_exon	Exon 4 of 6

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		9.1

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: chr15-78838089;