Variant 15-78544920-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002789.6(PSMA4):c.339G>A(p.Ala113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,610,976 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 99 hom. )

Consequence

PSMA4
NM_002789.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.24

Variant links:

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

PSMA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 15-78544920-G-A is Benign according to our data. Variant chr15-78544920-G-A is described in ClinVar as [Benign]. Clinvar id is 778997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00717 (1092/152208) while in subpopulation AMR AF= 0.0182 (278/15288). AF 95% confidence interval is 0.0164. There are 7 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA4	NM_002789.6 linkuse as main transcript	c.339G>A	p.Ala113=	synonymous_variant	6/9	ENST00000044462.12	NP_002780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA4	ENST00000044462.12 linkuse as main transcript	c.339G>A	p.Ala113=	synonymous_variant	6/9	1	NM_002789.6	ENSP00000044462	P1	P25789-1

Frequencies

GnomAD3 genomes

AF:

0.00719

AC:

1093

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00454

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00953

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.0105

AC:

2633

AN:

249784

Hom.:

AF XY:

0.00920

AC XY:

1242

AN XY:

134968

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0427

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00844

Gnomad OTH exome

AF:

0.00821

GnomAD4 exome

AF:

0.00805

AC:

11747

AN:

1458768

Hom.:

Cov.:

AF XY:

0.00772

AC XY:

5603

AN XY:

725626

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.0395

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.00350

Gnomad4 NFE exome

AF:

0.00823

Gnomad4 OTH exome

AF:

0.00674

GnomAD4 genome

AF:

0.00717

AC:

1092

AN:

152208

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

530

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00205

Gnomad4 AMR

AF:

0.0182

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00454

Gnomad4 NFE

AF:

0.00953

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00696

Hom.:

Bravo

AF:

0.00848

Asia WGS

AF:

0.00145

AC:

AN:

3474

EpiCase

AF:

0.00730

EpiControl

AF:

0.00689

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.3

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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