dbSNP rs2295827: PSMC6:c.86-46C>T (chr14-52708263-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.449

Publications

13 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002806.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSMC6	NM_002806.5	MANE Select	c.86-46C>T	intron	N/A	NP_002797.4
PSMC6	NM_001366414.2		c.-1744-46C>T	intron	N/A	NP_001353343.1
PSMC6	NR_158967.2		n.106-46C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PSMC6	ENST00000445930.7	TSL:1 MANE Select	c.86-46C>T	intron	N/A	ENSP00000401802.3	P62333
PSMC6	ENST00000612399.4	TSL:1	c.128-46C>T	intron	N/A	ENSP00000484998.1	A0A087X2I1
PSMC6	ENST00000554952.5	TSL:1	n.104-46C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0921

AC:

13990

AN:

151962

Hom.:

701

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.100

AC XY:

68570

AN XY:

683900

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

6001

12002

18004

24005

30006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3522

7044

10566

14088

17610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0921

AC:

14005

AN:

152080

Hom.:

702

Cov.:

AF XY:

0.0929

AC XY:

6903

AN XY:

74336

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6896

AN:

68002

Other (OTH)

AF:

0.0828

AC:

175

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

638

1277

1915

2554

3192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

(source)

DANN

Benign

0.73

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over