rs2295827

Variant names:

• chr14-52708263-C-T
• rs2295827
• NM_002806.5:c.86-46C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSMC6	NM_002806.5	c.86-46C>T		intron_variant	Intron 1 of 13	ENST00000445930.7	NP_002797.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMC6	ENST00000445930.7	c.86-46C>T		intron_variant	Intron 1 of 13	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

GnomAD2 exomes AF: 0.0960 AC: 23371 AN: 243556 AF XY: 0.0985

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 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

African (AFR) AF: 0.0699 AC: 2167 AN: 31004

American (AMR) AF: 0.0504 AC: 2230 AN: 44282

Ashkenazi Jewish (ASJ) AF: 0.0457 AC: 1167 AN: 25528

East Asian (EAS) AF: 0.151 AC: 5873 AN: 38870

South Asian (SAS) AF: 0.138 AC: 11494 AN: 83384

European-Finnish (FIN) AF: 0.113 AC: 5981 AN: 53018

Middle Eastern (MID) AF: 0.0554 AC: 277 AN: 4996

European-Non Finnish (NFE) AF: 0.0978 AC: 100414 AN: 1026756

Other (OTH) AF: 0.0919 AC: 5248 AN: 57134

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

African (AFR) AF: 0.0758 AC: 3145 AN: 41474

American (AMR) AF: 0.0606 AC: 926 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3472

East Asian (EAS) AF: 0.141 AC: 730 AN: 5180

South Asian (SAS) AF: 0.143 AC: 690 AN: 4814

European-Finnish (FIN) AF: 0.112 AC: 1183 AN: 10548

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6896 AN: 68002

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0893 Hom.: 883

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
PhyloP100		-0.45
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: rs2295827; hg19: chr14-53174981; COSMIC: COSV71628498; COSMIC: COSV71628498;