Genetic Variant PSMD1:c.1883+17659A>C (chr2-231104840-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002807.4(PSMD1):c.1883+17659A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,988 control chromosomes in the GnomAD database, including 21,823 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 0.49 ( 21823 hom., cov: 32)

Consequence

PSMD1
NM_002807.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.64

Publications

6 publications found

Variant links:

Genes affected

PSMD1 (HGNC:9554): (proteasome 26S subunit, non-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 the largest non-ATPase subunit of the 19S regulator lid, which is responsible for substrate recognition and binding. There is evidence that this proteasome and its subunits interact with viral proteins, including those of coronaviruses. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Aug 2020]

PSMD1 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PSMD1	NM_002807.4 link	c.1883+17659A>C	intron_variant	Intron 16 of 24	ENST00000308696.11	NP_002798.2	Q99460-1
PSMD1	NM_001191037.2 link	c.1883+17659A>C	intron_variant	Intron 16 of 23		NP_001177966.1	Q99460-2
PSMD1	NR_034059.2 link	n.1872+17659A>C	intron_variant	Intron 15 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD1	ENST00000308696.11 link	c.1883+17659A>C		intron_variant	Intron 16 of 24	1	NM_002807.4	ENSP00000309474.6		Q99460-1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74626

AN:

151870

Hom.:

21772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.811

Gnomad AMI

AF:

0.376

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.492

AC:

74732

AN:

151988

Hom.:

21823

Cov.:

AF XY:

0.494

AC XY:

36699

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.811

AC:

33646

AN:

41478

American (AMR)

AF:

0.375

AC:

5725

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

1447

AN:

3470

East Asian (EAS)

AF:

0.617

AC:

3194

AN:

5178

South Asian (SAS)

AF:

0.442

AC:

2135

AN:

4828

European-Finnish (FIN)

AF:

0.456

AC:

4808

AN:

10534

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.329

AC:

22328

AN:

67914

Other (OTH)

AF:

0.461

AC:

971

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1583

3166

4750

6333

7916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.366

Hom.:

14320

Bravo

AF:

0.498

Asia WGS

AF:

0.582

AC:

2022

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.60

(source)

DANN

Benign

0.63

PhyloP100

-2.6

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over