15-78542347-A-T

Variant names:

• chr15-78542347-A-T
• rs2292117
• NM_002789.6:c.46+128A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002789.6(PSMA4):​c.46+128A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000816 in 1,225,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: PSMA4 NM_002789.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 27 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.46+128A>T		intron	N/A	NP_002780.1	P25789-1
	PSMA4	NM_001102667.2		c.46+128A>T		intron	N/A	NP_001096137.1	P25789-1
	PSMA4	NM_001330676.2		c.46+128A>T		intron	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.46+128A>T		intron	N/A	ENSP00000044462.7	P25789-1
	PSMA4	ENST00000413382.6	TSL:1	c.-5+128A>T		intron	N/A	ENSP00000402118.2	P25789-2
	PSMA4	ENST00000558635.1	TSL:1	n.524A>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.16e-7 AC: 1 AN: 1225466 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 613248

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26972

American (AMR) AF: 0.00 AC: 0 AN: 29270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20394

East Asian (EAS) AF: 0.00 AC: 0 AN: 38392

South Asian (SAS) AF: 0.00 AC: 0 AN: 69184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5056

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 933862

Other (OTH) AF: 0.00 AC: 0 AN: 51746

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 15009

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.92
DANN	Benign	0.39
PhyloP100		-0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2292117; hg19: chr15-78834689;