rs2057168

Variant names:

• chr20-62137291-G-A
• rs2057168
• NM_002792.4:c.654+73C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-62137291-G-A
• chr20-62137291-G-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.654+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,468,850 control chromosomes in the GnomAD database, including 442,777 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 (35049 hom., cov: 32)
  • Exomes 𝑓: 0.78 (407728 hom.)
• Consequence: PSMA7 NM_002792.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 12 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=-0.88).
• 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 rank	MANE	Protein	UniProt
PSMA7	NM_002792.4	c.654+73C>T		intron_variant	Intron 6 of 6	ENST00000370873.9	NP_002783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA7	ENST00000370873.9	c.654+73C>T		intron_variant	Intron 6 of 6	1	NM_002792.4	ENSP00000359910.4

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96427 AN: 151946 Hom.: 35051 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.781 AC: 1028667 AN: 1316786 Hom.: 407728 AF XY: 0.782 AC XY: 518601 AN XY: 662900

African (AFR) AF: 0.215 AC: 6415 AN: 29888

American (AMR) AF: 0.737 AC: 29869 AN: 40540

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 17895 AN: 24858

East Asian (EAS) AF: 0.809 AC: 31596 AN: 39042

South Asian (SAS) AF: 0.765 AC: 63136 AN: 82486

European-Finnish (FIN) AF: 0.803 AC: 42817 AN: 53302

Middle Eastern (MID) AF: 0.762 AC: 4225 AN: 5546

European-Non Finnish (NFE) AF: 0.802 AC: 790590 AN: 985646

Other (OTH) AF: 0.759 AC: 42124 AN: 55478

GnomAD4 genome AF: 0.634 AC: 96440 AN: 152064 Hom.: 35049 Cov.: 32 AF XY: 0.638 AC XY: 47449 AN XY: 74352

African (AFR) AF: 0.241 AC: 9985 AN: 41440

American (AMR) AF: 0.719 AC: 10979 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2469 AN: 3466

East Asian (EAS) AF: 0.779 AC: 4036 AN: 5178

South Asian (SAS) AF: 0.749 AC: 3615 AN: 4828

European-Finnish (FIN) AF: 0.799 AC: 8449 AN: 10570

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54421 AN: 67990

Other (OTH) AF: 0.689 AC: 1457 AN: 2114

Alfa AF: 0.750 Hom.: 21574

Bravo AF: 0.612

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.52
PhyloP100		-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: rs2057168; hg19: chr20-60712347;