Variant rs1048990 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002791.3(PSMA6):c.-8C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,878 control chromosomes in the GnomAD database, including 26,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2134 hom., cov: 33)

Exomes 𝑓: 0.18 ( 23956 hom. )

Consequence

PSMA6
NM_002791.3 5_prime_UTR

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.965

Variant links:

Genes affected

PSMA6 (HGNC:9535): (proteasome 20S subunit alpha 6) 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. Multiple transcript variants encoding several different isoforms have been found for this gene. A pseudogene has been identified on the Y chromosome. [provided by RefSeq, Aug 2013]

PSMA6 links:

PRORP-PSMA6 (HGNC:):

PRORP-PSMA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 14-35292469-C-G is Benign according to our data. Variant chr14-35292469-C-G is described in ClinVar as [Benign, risk_factor]. Clinvar id is 6796.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA6	NM_002791.3 linkuse as main transcript	c.-8C>G		5_prime_UTR_variant	1/7	ENST00000261479.9	NP_002782.1
PRORP-PSMA6	NR_182666.1 linkuse as main transcript	n.3151+13751C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA6	ENST00000261479.9 linkuse as main transcript	c.-8C>G		5_prime_UTR_variant	1/7	1	NM_002791.3	ENSP00000261479	P1	P60900-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22916

AN:

152146

Hom.:

2133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0560

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.188

AC:

47053

AN:

250420

Hom.:

5020

AF XY:

0.190

AC XY:

25737

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.369

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.175

AC:

255623

AN:

1460614

Hom.:

23956

Cov.:

AF XY:

0.176

AC XY:

128235

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.0510

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.151

AC:

22921

AN:

152264

Hom.:

2134

Cov.:

AF XY:

0.153

AC XY:

11400

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0558

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.145

Hom.:

611

Bravo

AF:

0.150

Asia WGS

AF:

0.298

AC:

1033

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.171

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSMA6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Myocardial infarction, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.1

DANN

Benign

0.61

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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