20-62137455-A-G

Variant names:

• chr20-62137455-A-G
• rs2281740
• NM_002792.4:c.592-29T>C

Variant summary

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

The NM_002792.4(PSMA7):​c.592-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,610,320 control chromosomes in the GnomAD database, including 499,506 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 0.71 (39686 hom., cov: 31)
  • Exomes 𝑓: 0.79 (459820 hom.)
• Consequence: PSMA7 NM_002792.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 25 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002792.4. 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
	PSMA7	NM_002792.4	MANE Select	c.592-29T>C		intron	N/A	NP_002783.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA7	ENST00000370873.9	TSL:1 MANE Select	c.592-29T>C		intron	N/A	ENSP00000359910.4
	PSMA7	ENST00000442551.5	TSL:3	c.377T>C	p.Val126Ala	missense	Exon 4 of 5	ENSP00000397047.1
	PSMA7	ENST00000370861.1	TSL:5	c.382-29T>C		intron	N/A	ENSP00000359898.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107958 AN: 151904 Hom.: 39675 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.743

GnomAD2 exomes AF: 0.768 AC: 192870 AN: 251262 AF XY: 0.774

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.757

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.779

Gnomad FIN exome AF: 0.800

Gnomad NFE exome AF: 0.807

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.792 AC: 1155141 AN: 1458298 Hom.: 459820 Cov.: 32 AF XY: 0.792 AC XY: 575006 AN XY: 725746

African (AFR) AF: 0.486 AC: 16214 AN: 33356

American (AMR) AF: 0.758 AC: 33849 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 19194 AN: 26108

East Asian (EAS) AF: 0.809 AC: 32102 AN: 39680

South Asian (SAS) AF: 0.767 AC: 66099 AN: 86186

European-Finnish (FIN) AF: 0.805 AC: 42976 AN: 53402

Middle Eastern (MID) AF: 0.789 AC: 4546 AN: 5760

European-Non Finnish (NFE) AF: 0.805 AC: 893121 AN: 1108888

Other (OTH) AF: 0.781 AC: 47040 AN: 60260

GnomAD4 genome AF: 0.711 AC: 108014 AN: 152022 Hom.: 39686 Cov.: 31 AF XY: 0.712 AC XY: 52906 AN XY: 74308

African (AFR) AF: 0.498 AC: 20617 AN: 41394

American (AMR) AF: 0.748 AC: 11436 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2517 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4039 AN: 5178

South Asian (SAS) AF: 0.750 AC: 3618 AN: 4824

European-Finnish (FIN) AF: 0.800 AC: 8451 AN: 10558

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54741 AN: 68002

Other (OTH) AF: 0.743 AC: 1561 AN: 2102

Alfa AF: 0.754 Hom.: 80145

Bravo AF: 0.698

Asia WGS AF: 0.747 AC: 2597 AN: 3478

EpiCase AF: 0.807

EpiControl AF: 0.805

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.85
PhyloP100		-0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2281740; hg19: chr20-60712511;