rs2295827

Positions:

• chr14-52708263-C-T

Variant summary

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

The NM_002806.5(PSMC6):​c.86-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,517,052 control chromosomes in the GnomAD database, including 7,972 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 0.092 (702 hom., cov: 32)
  • Exomes 𝑓: 0.099 (7270 hom.)
• Consequence: PSMC6 NM_002806.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMC6	NM_002806.5	c.86-46C>T		intron_variant		ENST00000445930.7	NP_002797.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMC6	ENST00000445930.7	c.86-46C>T		intron_variant		1	NM_002806.5	ENSP00000401802.3

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13990 AN: 151962 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0813

GnomAD3 exomes AF: 0.0960 AC: 23371 AN: 243556 Hom.: 1336 AF XY: 0.0985 AC XY: 13028 AN XY: 132208

Gnomad AFR exome AF: 0.0724

Gnomad AMR exome AF: 0.0484

Gnomad ASJ exome AF: 0.0470

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0971

Gnomad OTH exome AF: 0.0813

GnomAD4 exome AF: 0.0988 AC: 134851 AN: 1364972 Hom.: 7270 Cov.: 23 AF XY: 0.100 AC XY: 68570 AN XY: 683900

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.0457

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.0978

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0921 AC: 14005 AN: 152080 Hom.: 702 Cov.: 32 AF XY: 0.0929 AC XY: 6903 AN XY: 74336

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0897 Hom.: 695

Bravo AF: 0.0860

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.73

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: rs2295827; hg19: chr14-53174981; COSMIC: COSV71628498; COSMIC: COSV71628498;