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GeneBe

15-78544920-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.24 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PSMA4NM_002789.6 linkuse as main transcriptc.339G>A p.Ala113= synonymous_variant 6/9 ENST00000044462.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PSMA4ENST00000044462.12 linkuse as main transcriptc.339G>A p.Ala113= synonymous_variant 6/91 NM_002789.6 P1P25789-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00719
AC:
1093
AN:
152090
Hom.:
7
Cov.:
33
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.:
48
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.:
99
Cov.:
29
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00717
AC:
1092
AN:
152208
Hom.:
7
Cov.:
33
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.:
1
Bravo
AF:
0.00848
Asia WGS
AF:
0.00145
AC:
5
AN:
3474
EpiCase
AF:
0.00730
EpiControl
AF:
0.00689

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 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.

Other links and lift over

dbSNP: rs11551774; hg19: chr15-78837262; API