20-62137228-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002792.4(PSMA7):​c.654+136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.654+136C>G		intron	N/A	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.654+136C>G		intron	N/A	ENSP00000359910.4	O14818-1
	PSMA7	ENST00000867843.1		c.642+136C>G		intron	N/A	ENSP00000537902.1
	PSMA7	ENST00000931805.1		c.636+136C>G		intron	N/A	ENSP00000601864.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 828554 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 434680

African (AFR) AF: 0.00 AC: 0 AN: 19446

American (AMR) AF: 0.00 AC: 0 AN: 30802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20634

East Asian (EAS) AF: 0.00 AC: 0 AN: 36430

South Asian (SAS) AF: 0.00 AC: 0 AN: 68736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 559722

Other (OTH) AF: 0.00 AC: 0 AN: 39488

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 22381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.64
DANN	Benign	0.50
PhyloP100		-0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2057169;

hg19: chr20-60712284;