20-62138276-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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=-0.32).
• BP6: Variant 20-62138276-A-G is Benign according to our data. Variant chr20-62138276-A-G is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA7	NM_002792.4	c.486T>C	p.Gly162Gly	synonymous_variant	Exon 5 of 7	ENST00000370873.9	NP_002783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA7	ENST00000370873.9	c.486T>C	p.Gly162Gly	synonymous_variant	Exon 5 of 7	1	NM_002792.4	ENSP00000359910.4

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

GnomAD3 exomes AF: 0.850 AC: 211350 AN: 248630 Hom.: 89953 AF XY: 0.848 AC XY: 113903 AN XY: 134386

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 SAS exome AF: 0.815

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

Gnomad4 AFR exome AF: 0.910

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.862

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.827

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.860

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

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.883

Alfa AF: 0.863 Hom.: 65781

Bravo AF: 0.875

Asia WGS AF: 0.819 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.8
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs1135961; hg19: chr20-60713332;