rs2295826

Positions:

• chr14-52708205-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002806.5(PSMC6):​c.86-104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 940,292 control chromosomes in the GnomAD database, including 5,836 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 0.11 (1021 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4815 hom.)
• Consequence: PSMC6 NM_002806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

Genes affected

PSMC6 (HGNC:9553): (proteasome 26S subunit, ATPase 6) 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. Pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, Jul 2008]

PSMC6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMC6	NM_002806.5	c.86-104A>G		intron_variant		ENST00000445930.7	NP_002797.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMC6	ENST00000445930.7	c.86-104A>G		intron_variant		1	NM_002806.5	ENSP00000401802.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17070 AN: 152124 Hom.: 1019 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0938

GnomAD4 exome AF: 0.105 AC: 82604 AN: 788048 Hom.: 4815 AF XY: 0.106 AC XY: 43203 AN XY: 407440

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0599

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0992

GnomAD4 genome AF: 0.112 AC: 17091 AN: 152244 Hom.: 1021 Cov.: 32 AF XY: 0.112 AC XY: 8371 AN XY: 74410

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0951

Alfa AF: 0.0947 Hom.: 751

Bravo AF: 0.109

Asia WGS AF: 0.140 AC: 487 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2295826; hg19: chr14-53174923; COSMIC: COSV71628821; COSMIC: COSV71628821;