7-103352638-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002803.4(PSMC2):c.71-1283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 495,342 control chromosomes in the GnomAD database, including 10,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2633 hom., cov: 31)
  • Exomes 𝑓: 0.19 (7557 hom.)
• Consequence: PSMC2 NM_002803.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

Genes affected

PSMC2 (HGNC:9548): (proteasome 26S subunit, ATPase 2) 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. This subunit has been shown to interact with several of the basal transcription factors so, in addition to participation in proteasome functions, this subunit may participate in the regulation of transcription. This subunit may also compete with PSMC3 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-103352638-C-T is Benign according to our data. Variant chr7-103352638-C-T is described in ClinVar as [Benign]. Clinvar id is 1249288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMC2	NM_002803.4	c.71-1283C>T		intron_variant		ENST00000292644.5
PSMC2	NM_001204453.1	c.71-1283C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC2	ENST00000292644.5	c.71-1283C>T		intron_variant		1	NM_002803.4	P3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24809 AN: 151926 Hom.: 2635 Cov.: 31

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.191 AC: 65501 AN: 343298 Hom.: 7557 AF XY: 0.184 AC XY: 33886 AN XY: 184244

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.000473

Gnomad4 SAS exome AF: 0.0869

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.163 AC: 24807 AN: 152044 Hom.: 2633 Cov.: 31 AF XY: 0.159 AC XY: 11827 AN XY: 74298

Gnomad4 AFR AF: 0.0491

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.181

Alfa AF: 0.205 Hom.: 453

Bravo AF: 0.155

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.3
Dann	Benign	0.67

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: rs35850434; hg19: chr7-102993085;