Genetic Variant NM_002788.4:c.565G>T (chr14-58267495-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002788.4(PSMA3):c.565G>T(p.Asp189Tyr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSMA3
NM_002788.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.12

Publications

0 publications found

Variant links:

Genes affected

PSMA3 (HGNC:9532): (proteasome 20S subunit alpha 3) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 a member of the peptidase T1A family, that is a 20S core alpha subunit. Two alternative transcripts encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PSMA3 links:

PSMA3-AS1 (HGNC:26445): (PSMA3 antisense RNA 1)

PSMA3-AS1 links:

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARMH4 links:

ENSG00000258682 (HGNC:):

ENSG00000258682 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002788.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMA3	NM_002788.4	MANE Select	c.565G>T	p.Asp189Tyr	missense	Exon 8 of 11	NP_002779.1	A0A140VK43
PSMA3	NM_152132.3		c.544G>T	p.Asp182Tyr	missense	Exon 8 of 11	NP_687033.1	P25788-2
PSMA3	NR_038123.2		n.560G>T		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMA3	ENST00000216455.9	TSL:1 MANE Select	c.565G>T	p.Asp189Tyr	missense	Exon 8 of 11	ENSP00000216455.4	P25788-1
PSMA3	ENST00000412908.6	TSL:1	c.544G>T	p.Asp182Tyr	missense	Exon 8 of 11	ENSP00000390491.2	P25788-2
PSMA3-AS1	ENST00000554360.5	TSL:1	n.447-102C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1419306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704774

African (AFR)

AF:

0.00

AC:

AN:

31434

American (AMR)

AF:

0.00

AC:

AN:

36070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25044

East Asian (EAS)

AF:

0.00

AC:

AN:

37884

South Asian (SAS)

AF:

0.00

AC:

AN:

76154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095990

Other (OTH)

AF:

0.00

AC:

AN:

58662

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.5

PhyloP100

9.1

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.83

MutPred

0.71

Gain of MoRF binding (P = 0.0482)

MVP

0.70

MPC

2.3

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.69

Mutation Taster

=29/71

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over