rs3746651

Positions:

• chr20-62143364-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370873.9(PSMA7):​c.-61G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,006,390 control chromosomes in the GnomAD database, including 305,654 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 0.63 (34017 hom., cov: 33)
  • Exomes 𝑓: 0.79 (271637 hom.)
• Consequence: PSMA7 ENST00000370873.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868

Genes affected

PSMA7 (HGNC:9536): (proteasome 20S subunit alpha 7) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. This gene encodes a member of the peptidase T1A family that functions as a 20S core alpha subunit. The encoded protein interacts with the hepatitis B virus X protein and plays a role in regulating hepatitis C virus internal ribosome entry site (IRES) activity, an activity essential for viral replication. The encoded protein also plays a role in the cellular stress response by regulating hypoxia-inducible factor-1alpha. A pseudogene of this gene is located on the long arm of chromosome 9. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA7	NM_002792.4	c.-61G>A		5_prime_UTR_variant	1/7	ENST00000370873.9	NP_002783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA7	ENST00000370873.9	c.-61G>A		5_prime_UTR_variant	1/7	1	NM_002792.4	ENSP00000359910	P1
PSMA7	ENST00000370858.3	c.-61G>A		5_prime_UTR_variant	1/3	2		ENSP00000359895
PSMA7	ENST00000484488.5	n.77G>A		non_coding_transcript_exon_variant	1/7	3

Frequencies

GnomAD3 genomes AF: 0.632 AC: 93880 AN: 148596 Hom.: 34020 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.791 AC: 678389 AN: 857688 Hom.: 271637 Cov.: 11 AF XY: 0.792 AC XY: 330313 AN XY: 416982

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.761

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.631 AC: 93892 AN: 148702 Hom.: 34017 Cov.: 33 AF XY: 0.635 AC XY: 46007 AN XY: 72506

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.687

Alfa AF: 0.691 Hom.: 4894

Bravo AF: 0.613

Asia WGS AF: 0.691 AC: 2085 AN: 3022

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs3746651; hg19: chr20-60718420; COSMIC: COSV105236232; COSMIC: COSV105236232;