rs1218649086

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002788.4(PSMA3):c.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A12A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PSMA3
NM_002788.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Publications

1 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:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.761

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.35C>T	p.Ala12Val	missense	Exon 2 of 11	NP_002779.1	A0A140VK43
PSMA3	NM_152132.3		c.35C>T	p.Ala12Val	missense	Exon 2 of 11	NP_687033.1	P25788-2
PSMA3	NR_038123.2		n.99+2822C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMA3	ENST00000216455.9	TSL:1 MANE Select	c.35C>T	p.Ala12Val	missense	Exon 2 of 11	ENSP00000216455.4	P25788-1
PSMA3	ENST00000412908.6	TSL:1	c.35C>T	p.Ala12Val	missense	Exon 2 of 11	ENSP00000390491.2	P25788-2
PSMA3	ENST00000925587.1		c.35C>T	p.Ala12Val	missense	Exon 2 of 12	ENSP00000595646.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249694

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451948

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722866

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33120

American (AMR)

AF:

0.00

AC:

AN:

44250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00

AC:

AN:

39588

South Asian (SAS)

AF:

0.00

AC:

AN:

85652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104156

Other (OTH)

AF:

0.00

AC:

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

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

0.85

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.14

PhyloP100

7.5

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.31

Sift

Benign

0.46

Sift4G

Benign

1.0

Polyphen

1.0

Vest4

0.78

MutPred

0.36

Loss of disorder (P = 0.0787)

MVP

0.71

MPC

1.2

ClinPred

0.68

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.75

gMVP

0.72

Mutation Taster

=20/80

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over