15-78552044-T-C

Variant names:

• chr15-78552044-T-C
• rs905740
• NM_002789.6:c.*3100T>C

Variant summary

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

The NM_002789.6(PSMA4):​c.*3100T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,072 control chromosomes in the GnomAD database, including 34,562 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 0.67 (34562 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSMA4 NM_002789.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	NM_002789.6	MANE Select	c.*3100T>C		3_prime_UTR	Exon 9 of 9	NP_002780.1
	PSMA4	NM_001330676.2		c.*3100T>C		3_prime_UTR	Exon 9 of 9	NP_001317605.1
	PSMA4	NM_001330675.2		c.*3100T>C		3_prime_UTR	Exon 9 of 9	NP_001317604.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA4	ENST00000044462.12	TSL:1 MANE Select	c.*3100T>C		3_prime_UTR	Exon 9 of 9	ENSP00000044462.7

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101318 AN: 151952 Hom.: 34518 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.677

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.667 AC: 101421 AN: 152072 Hom.: 34562 Cov.: 33 AF XY: 0.671 AC XY: 49894 AN XY: 74334

African (AFR) AF: 0.773 AC: 32055 AN: 41492

American (AMR) AF: 0.760 AC: 11602 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2242 AN: 3466

East Asian (EAS) AF: 0.837 AC: 4330 AN: 5176

South Asian (SAS) AF: 0.668 AC: 3221 AN: 4820

European-Finnish (FIN) AF: 0.623 AC: 6569 AN: 10552

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39230 AN: 67984

Other (OTH) AF: 0.675 AC: 1426 AN: 2112

Alfa AF: 0.645 Hom.: 9265

Bravo AF: 0.682

Asia WGS AF: 0.729 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-1.2

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: rs905740; hg19: chr15-78844386;