NM_002792.4:c.654+136C>T

Variant names:

• chr20-62137228-G-A
• rs2057169
• NM_002792.4:c.654+136C>T

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+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 979,678 control chromosomes in the GnomAD database, including 290,674 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 (35062 hom., cov: 32)
  • Exomes 𝑓: 0.78 (255612 hom.)
• Consequence: PSMA7 NM_002792.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 8 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=-0.84).
• 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+136C>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+136C>T		intron_variant	Intron 6 of 6	1	NM_002792.4	ENSP00000359910.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96457 AN: 152054 Hom.: 35064 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: 0.691

GnomAD4 exome AF: 0.780 AC: 645496 AN: 827506 Hom.: 255612 AF XY: 0.781 AC XY: 339126 AN XY: 434160

African (AFR) AF: 0.224 AC: 4349 AN: 19432

American (AMR) AF: 0.738 AC: 22700 AN: 30760

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 14848 AN: 20610

East Asian (EAS) AF: 0.812 AC: 29566 AN: 36408

South Asian (SAS) AF: 0.767 AC: 52691 AN: 68664

European-Finnish (FIN) AF: 0.803 AC: 39196 AN: 48812

Middle Eastern (MID) AF: 0.757 AC: 3361 AN: 4438

European-Non Finnish (NFE) AF: 0.803 AC: 448886 AN: 558950

Other (OTH) AF: 0.758 AC: 29899 AN: 39432

GnomAD4 genome AF: 0.634 AC: 96470 AN: 152172 Hom.: 35062 Cov.: 32 AF XY: 0.638 AC XY: 47467 AN XY: 74398

African (AFR) AF: 0.240 AC: 9972 AN: 41490

American (AMR) AF: 0.719 AC: 10989 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2470 AN: 3468

East Asian (EAS) AF: 0.780 AC: 4049 AN: 5192

South Asian (SAS) AF: 0.749 AC: 3613 AN: 4824

European-Finnish (FIN) AF: 0.799 AC: 8464 AN: 10594

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

European-Non Finnish (NFE) AF: 0.800 AC: 54428 AN: 68000

Other (OTH) AF: 0.691 AC: 1456 AN: 2108

Alfa AF: 0.752 Hom.: 22381

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	-0.84
CADD	Benign	0.80
DANN	Benign	0.71
PhyloP100		-0.61
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: rs2057169; hg19: chr20-60712284;