20-62138276-A-G

Variant names:

• chr20-62138276-A-G
• rs1135961
• NM_002792.4:c.486T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4 BP7 BA1

The NM_002792.4(PSMA7):​c.486T>C​(p.Gly162Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,611,052 control chromosomes in the GnomAD database, including 590,612 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 0.87 (57366 hom., cov: 35)
  • Exomes 𝑓: 0.85 (533246 hom.)
• Consequence: PSMA7 NM_002792.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383
• Publications: 29 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.29).
• BP7: Synonymous conserved (PhyloP=0.383 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA7	NM_002792.4	MANE Select	c.486T>C	p.Gly162Gly	synonymous	Exon 5 of 7	NP_002783.1	O14818-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA7	ENST00000370873.9	TSL:1 MANE Select	c.486T>C	p.Gly162Gly	synonymous	Exon 5 of 7	ENSP00000359910.4	O14818-1
	PSMA7	ENST00000867843.1		c.474T>C	p.Gly158Gly	synonymous	Exon 5 of 7	ENSP00000537902.1
	PSMA7	ENST00000931805.1		c.468T>C	p.Gly156Gly	synonymous	Exon 5 of 7	ENSP00000601864.1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132058 AN: 152184 Hom.: 57324 Cov.: 35

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.885

GnomAD2 exomes AF: 0.850 AC: 211350 AN: 248630 AF XY: 0.848

Gnomad AFR exome AF: 0.907

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.832

Gnomad EAS exome AF: 0.828

Gnomad FIN exome AF: 0.822

Gnomad NFE exome AF: 0.860

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.855 AC: 1246616 AN: 1458750 Hom.: 533246 Cov.: 53 AF XY: 0.853 AC XY: 619275 AN XY: 725596

African (AFR) AF: 0.910 AC: 30445 AN: 33460

American (AMR) AF: 0.860 AC: 38282 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 21493 AN: 25836

East Asian (EAS) AF: 0.862 AC: 34169 AN: 39656

South Asian (SAS) AF: 0.817 AC: 70242 AN: 85938

European-Finnish (FIN) AF: 0.827 AC: 43990 AN: 53220

Middle Eastern (MID) AF: 0.884 AC: 5083 AN: 5750

European-Non Finnish (NFE) AF: 0.857 AC: 951091 AN: 1110108

Other (OTH) AF: 0.860 AC: 51821 AN: 60254

GnomAD4 genome AF: 0.868 AC: 132158 AN: 152302 Hom.: 57366 Cov.: 35 AF XY: 0.865 AC XY: 64379 AN XY: 74462

African (AFR) AF: 0.908 AC: 37749 AN: 41580

American (AMR) AF: 0.873 AC: 13360 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2909 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4280 AN: 5164

South Asian (SAS) AF: 0.806 AC: 3895 AN: 4832

European-Finnish (FIN) AF: 0.820 AC: 8692 AN: 10604

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58315 AN: 68028

Other (OTH) AF: 0.883 AC: 1863 AN: 2110

Alfa AF: 0.864 Hom.: 94422

Bravo AF: 0.875

Asia WGS AF: 0.819 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.8
DANN	Benign	0.80
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=80/20	polymorphism

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: rs1135961; hg19: chr20-60713332; COSMIC: COSV108055019; COSMIC: COSV108055019;