Genetic Variant NM_002807.4:c.1402G>T (chr2-231080303-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002807.4(PSMD1):c.1402G>T(p.Ala468Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A468T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PSMD1
NM_002807.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.82

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37124595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002807.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMD1	NM_002807.4	MANE Select	c.1402G>T	p.Ala468Ser	missense	Exon 12 of 25	NP_002798.2
PSMD1	NM_001191037.2		c.1402G>T	p.Ala468Ser	missense	Exon 12 of 24	NP_001177966.1	Q99460-2
PSMD1	NR_034059.2		n.1391G>T		non_coding_transcript_exon	Exon 11 of 24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMD1	ENST00000308696.11	TSL:1 MANE Select	c.1402G>T	p.Ala468Ser	missense	Exon 12 of 25	ENSP00000309474.6	Q99460-1
PSMD1	ENST00000431051.6	TSL:1	n.*1085G>T		non_coding_transcript_exon	Exon 11 of 24	ENSP00000400483.1	F8WCE3
PSMD1	ENST00000431051.6	TSL:1	n.*1085G>T		3_prime_UTR	Exon 11 of 24	ENSP00000400483.1	F8WCE3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.026

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

9.8

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.98

REVEL

Benign

0.22

Sift

Benign

0.20

Sift4G

Benign

0.18

Polyphen

0.59

Vest4

0.53

MutPred

0.40

Gain of disorder (P = 0.0172)

MVP

0.48

MPC

0.95

ClinPred

0.91

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.47

Mutation Taster

=42/58

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over