chr1-109425788-A-C

Variant names:

• chr1-109425788-A-C
• rs3820667
• ENST00000538610.5:c.-608T>G

Variant summary

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

The ENST00000538610.5(PSMA5):​c.-608T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 153,836 control chromosomes in the GnomAD database, including 16,582 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 0.43 (16359 hom., cov: 32)
  • Exomes 𝑓: 0.50 (223 hom.)
• Consequence: PSMA5 ENST00000538610.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 13 publications found

Genes affected

PSMA5 (HGNC:9534): (proteasome 20S subunit alpha 5) 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. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000538610.5. 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
	PSMA5	NM_002790.4	MANE Select	c.29+514T>G		intron	N/A	NP_002781.2
	PSMA5	NM_001199772.2		c.-79+514T>G		intron	N/A	NP_001186701.1
	PSMA5	NM_001199773.2		c.-146+617T>G		intron	N/A	NP_001186702.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA5	ENST00000538610.5	TSL:1	c.-608T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000440618.1
	PSMA5	ENST00000490870.5	TSL:1	n.345T>G		non_coding_transcript_exon	Exon 1 of 9
	PSMA5	ENST00000538610.5	TSL:1	c.-608T>G		5_prime_UTR	Exon 1 of 9	ENSP00000440618.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65801 AN: 151936 Hom.: 16351 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.500 AC: 891 AN: 1782 Hom.: 223 Cov.: 0 AF XY: 0.513 AC XY: 507 AN XY: 988

African (AFR) AF: 0.152 AC: 10 AN: 66

American (AMR) AF: 0.578 AC: 67 AN: 116

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 20 AN: 44

East Asian (EAS) AF: 0.568 AC: 25 AN: 44

South Asian (SAS) AF: 0.410 AC: 100 AN: 244

European-Finnish (FIN) AF: 0.538 AC: 28 AN: 52

Middle Eastern (MID) AF: 1.00 AC: 6 AN: 6

European-Non Finnish (NFE) AF: 0.531 AC: 592 AN: 1114

Other (OTH) AF: 0.448 AC: 43 AN: 96

GnomAD4 genome AF: 0.433 AC: 65821 AN: 152054 Hom.: 16359 Cov.: 32 AF XY: 0.435 AC XY: 32349 AN XY: 74318

African (AFR) AF: 0.169 AC: 7013 AN: 41482

American (AMR) AF: 0.528 AC: 8058 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3222 AN: 5170

South Asian (SAS) AF: 0.478 AC: 2308 AN: 4826

European-Finnish (FIN) AF: 0.525 AC: 5545 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36061 AN: 67958

Other (OTH) AF: 0.466 AC: 980 AN: 2104

Alfa AF: 0.503 Hom.: 10728

Bravo AF: 0.424

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.52
PhyloP100		0.29
PromoterAI		-0.026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3820667; hg19: chr1-109968410;