NM_002802.3:c.345C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002802.3(PSMC1):c.345C>T(p.Ile115Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,056 control chromosomes in the GnomAD database, including 23,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23785 hom., cov: 32)

Exomes 𝑓: 0.59 ( 258474 hom. )

Failed GnomAD Quality Control

Consequence

PSMC1
NM_002802.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

Publications

21 publications found

Variant links:

Genes affected

PSMC1 (HGNC:9547): (proteasome 26S subunit, ATPase 1) 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. This subunit and a 20S core alpha subunit interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. This subunit also interacts with the adenovirus E1A protein and this interaction alters the activity of the proteasome. Finally, this subunit interacts with ataxin-7, suggesting a role for the proteasome in the development of spinocerebellar ataxia type 7, a progressive neurodegenerative disorder. [provided by RefSeq, Jul 2008]

PSMC1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P
neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PSMC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 14-90263727-C-T is Benign according to our data. Variant chr14-90263727-C-T is described in ClinVar as Benign. ClinVar VariationId is 1302301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002802.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMC1	NM_002802.3	MANE Select	c.345C>T	p.Ile115Ile	synonymous	Exon 5 of 11	NP_002793.2
	PSMC1	NM_001330212.2		c.126C>T	p.Ile42Ile	synonymous	Exon 6 of 12	NP_001317141.1	P62191-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMC1	ENST00000261303.13	TSL:1 MANE Select	c.345C>T	p.Ile115Ile	synonymous	Exon 5 of 11	ENSP00000261303.8	P62191-1
PSMC1	ENST00000906986.1		c.342C>T	p.Ile114Ile	synonymous	Exon 5 of 11	ENSP00000577045.1
PSMC1	ENST00000943594.1		c.345C>T	p.Ile115Ile	synonymous	Exon 5 of 11	ENSP00000613653.1

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83767

AN:

151938

Hom.:

23773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.592

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.581

GnomAD2 exomes

AF:

0.596

AC:

149327

AN:

250710

AF XY:

0.600

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.652

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.606

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.593

AC:

865202

AN:

1459156

Hom.:

258474

Cov.:

AF XY:

0.595

AC XY:

432306

AN XY:

726044

show subpopulations

African (AFR)

AF:

0.408

AC:

13631

AN:

33410

American (AMR)

AF:

0.648

AC:

28953

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

17664

AN:

26120

East Asian (EAS)

AF:

0.488

AC:

19352

AN:

39692

South Asian (SAS)

AF:

0.628

AC:

54132

AN:

86188

European-Finnish (FIN)

AF:

0.599

AC:

31978

AN:

53416

Middle Eastern (MID)

AF:

0.703

AC:

4038

AN:

5746

European-Non Finnish (NFE)

AF:

0.595

AC:

659678

AN:

1109592

Other (OTH)

AF:

0.593

AC:

35776

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

17559

35118

52678

70237

87796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17948

35896

53844

71792

89740

<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:

0.551

AC:

83823

AN:

152056

Hom.:

23785

Cov.:

AF XY:

0.553

AC XY:

41065

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.419

AC:

17388

AN:

41458

American (AMR)

AF:

0.625

AC:

9554

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

2371

AN:

3470

East Asian (EAS)

AF:

0.483

AC:

2496

AN:

5170

South Asian (SAS)

AF:

0.613

AC:

2957

AN:

4820

European-Finnish (FIN)

AF:

0.592

AC:

6258

AN:

10576

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.603

AC:

40947

AN:

67960

Other (OTH)

AF:

0.585

AC:

1237

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1903

3806

5708

7611

9514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.595

Hom.:

14305

Bravo

AF:

0.545

Asia WGS

AF:

0.561

AC:

1953

AN:

3478

EpiCase

AF:

0.612

EpiControl

AF:

0.612

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.5

Mutation Taster

=99/1

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