rs12878391

Variant names:

• chr14-35303372-A-G
• rs12878391
• NM_002791.3:c.77-4622A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002791.3(PSMA6):​c.77-4622A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,968 control chromosomes in the GnomAD database, including 4,270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4270 hom., cov: 32)
• Consequence: PSMA6 NM_002791.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 5 publications found

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]

ENSG00000258790 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA6	NM_002791.3	c.77-4622A>G		intron_variant	Intron 1 of 6	ENST00000261479.9	NP_002782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA6	ENST00000261479.9	c.77-4622A>G		intron_variant	Intron 1 of 6	1	NM_002791.3	ENSP00000261479.4
ENSG00000258790	ENST00000557565.1	n.*892-4622A>G		intron_variant	Intron 9 of 14	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35511 AN: 151850 Hom.: 4272 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35524 AN: 151968 Hom.: 4270 Cov.: 32 AF XY: 0.235 AC XY: 17475 AN XY: 74224

African (AFR) AF: 0.187 AC: 7746 AN: 41470

American (AMR) AF: 0.182 AC: 2776 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1030 AN: 5162

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4810

European-Finnish (FIN) AF: 0.349 AC: 3674 AN: 10520

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17646 AN: 67980

Other (OTH) AF: 0.226 AC: 476 AN: 2110

Alfa AF: 0.252 Hom.: 643

Bravo AF: 0.220

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.8
DANN	Benign	0.30
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12878391; hg19: chr14-35772578;