Variant chr14-35308904-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_002791.3(PSMA6):c.172-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,572,524 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

PSMA6
NM_002791.3 intron

Scores

Splicing: ADA: 0.6532

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.96

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:

ENSG00000258790 (HGNC:):

ENSG00000258790 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 14-35308904-T-G is Benign according to our data. Variant chr14-35308904-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3050747.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 405 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMA6	NM_002791.3 linkuse as main transcript	c.172-10T>G		intron_variant		ENST00000261479.9	NP_002782.1	P60900-1A0A140VK44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA6	ENST00000261479.9 linkuse as main transcript	c.172-10T>G		intron_variant		1	NM_002791.3	ENSP00000261479.4		P60900-1
ENSG00000258790	ENST00000557565.1 linkuse as main transcript	n.*987-10T>G		intron_variant		2		ENSP00000454657.1

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

404

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000703

AC:

166

AN:

235992

Hom.:

AF XY:

0.000570

AC XY:

AN XY:

127992

show subpopulations

Gnomad AFR exome

AF:

0.00984

Gnomad AMR exome

AF:

0.000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000222

AC:

315

AN:

1420184

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

140

AN XY:

707996

show subpopulations

Gnomad4 AFR exome

AF:

0.00840

Gnomad4 AMR exome

AF:

0.000431

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000277

Gnomad4 OTH exome

AF:

0.000440

GnomAD4 genome

AF:

0.00266

AC:

405

AN:

152340

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00916

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00306

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PSMA6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 22, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.65

dbscSNV1_RF

Benign

0.69

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