20-62137455-A-G

Position:

• chr20-62137455-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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]

PSMA7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-62137455-A-G is Benign according to our data. Variant chr20-62137455-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA7	NM_002792.4	c.592-29T>C		intron_variant		ENST00000370873.9	NP_002783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA7	ENST00000370873.9	c.592-29T>C		intron_variant		1	NM_002792.4	ENSP00000359910.4

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

GnomAD3 exomes AF: 0.768 AC: 192870 AN: 251262 Hom.: 74886 AF XY: 0.774 AC XY: 105098 AN XY: 135804

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 SAS exome AF: 0.763

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

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.758

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.809

Gnomad4 SAS exome AF: 0.767

Gnomad4 FIN exome AF: 0.805

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.781

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

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.743

Alfa AF: 0.776 Hom.: 57868

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2281740; hg19: chr20-60712511;