Genetic Variant PSMA3:c.544-6C>A (chr14-58267468-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002788.4(PSMA3):c.544-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSMA3
NM_002788.4 splice_region, intron

Scores

Splicing: ADA: 0.002464

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.317

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

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	Effect	Exon Rank	Protein	UniProt
PSMA3	NM_002788.4	MANE Select	c.544-6C>A	splice_region intron	N/A	NP_002779.1	A0A140VK43
PSMA3	NM_152132.3		c.523-6C>A	splice_region intron	N/A	NP_687033.1	P25788-2
PSMA3-AS1	NR_029434.1		n.455-75G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PSMA3	ENST00000216455.9	TSL:1 MANE Select	c.544-6C>A	splice_region intron	N/A	ENSP00000216455.4	P25788-1
PSMA3	ENST00000412908.6	TSL:1	c.523-6C>A	splice_region intron	N/A	ENSP00000390491.2	P25788-2
PSMA3-AS1	ENST00000554360.5	TSL:1	n.447-75G>T	intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1400724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695178

African (AFR)

AF:

0.00

AC:

AN:

30492

American (AMR)

AF:

0.00

AC:

AN:

31988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24218

East Asian (EAS)

AF:

0.00

AC:

AN:

37314

South Asian (SAS)

AF:

0.00

AC:

AN:

73544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088238

Other (OTH)

AF:

0.00

AC:

AN:

57762

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

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.0

(source)

DANN

Benign

0.67

PhyloP100

-0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0025

dbscSNV1_RF

Benign

0.11

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