Variant chr14-58267470-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002788.4(PSMA3):c.544-4A>G variant causes a splice region, splice polypyrimidine tract, 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PSMA3
NM_002788.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007118

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

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:

(HGNC:):

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-58267470-A-G is Benign according to our data. Variant chr14-58267470-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2869093.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMA3	NM_002788.4 linkuse as main transcript	c.544-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000216455.9
PSMA3-AS1	NR_029435.1 linkuse as main transcript	n.414-77T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PSMA3	ENST00000216455.9 linkuse as main transcript	c.544-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_002788.4	P4	P25788-1
PSMA3-AS1	ENST00000554360.5 linkuse as main transcript	n.447-77T>C	intron_variant, non_coding_transcript_variant	1
	ENST00000557322.1 linkuse as main transcript	n.456-2091A>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1405186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697378

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.8

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over