Genetic Variant ENST00000612399.4:c.16A>C (chr14-52707193-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000612399.4(PSMC6):c.16A>C(p.Ile6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000078 in 1,538,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

PSMC6
ENST00000612399.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34101278).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000612399.4. 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.-27A>C	upstream_gene	N/A	NP_002797.4
PSMC6	NM_001366414.2		c.-1856A>C	upstream_gene	N/A	NP_001353343.1
PSMC6	NR_158967.2		n.-7A>C	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMC6	ENST00000612399.4	TSL:1	c.16A>C	p.Ile6Leu	missense	Exon 1 of 14	ENSP00000484998.1	A0A087X2I1
PSMC6	ENST00000929612.1		c.-27A>C		5_prime_UTR	Exon 1 of 14	ENSP00000599671.1
PSMC6	ENST00000968040.1		c.-27A>C		5_prime_UTR	Exon 1 of 12	ENSP00000638099.1

Frequencies

GnomAD3 genomes

AF:

0.0000138

AC:

AN:

144714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000415

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000441

AC:

AN:

249668

AF XY:

0.0000444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000600

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000718

AC:

AN:

1393494

Hom.:

Cov.:

AF XY:

0.00000866

AC XY:

AN XY:

693176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31586

American (AMR)

AF:

0.00

AC:

AN:

42782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23614

East Asian (EAS)

AF:

0.000262

AC:

AN:

34304

South Asian (SAS)

AF:

0.00

AC:

AN:

85282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5372

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1070274

Other (OTH)

AF:

0.00

AC:

AN:

55810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000138

AC:

AN:

144714

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

70016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38800

American (AMR)

AF:

0.00

AC:

AN:

14182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.000415

AC:

AN:

4814

South Asian (SAS)

AF:

0.00

AC:

AN:

4376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66614

Other (OTH)

AF:

0.00

AC:

AN:

1988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000843

Hom.:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0029

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.34

MetaSVM

Uncertain

0.58

PhyloP100

5.7

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.19

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Benign

0.36

Vest4

0.60

MutPred

0.14

Gain of disorder (P = 0.0781)

MVP

0.71

MPC

0.015

ClinPred

0.98

GERP RS

5.4

PromoterAI

-0.40

Neutral

(source)

gMVP

0.16

Mutation Taster

=87/13

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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