rs2277460

Positions:

• chr14-35292367-C-A
• chr14-35292367-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_182666.1(PRORP-PSMA6):​n.3151+13649C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,527,866 control chromosomes in the GnomAD database, including 10,562 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 0.11 (940 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9622 hom.)
• Consequence: PRORP-PSMA6 NR_182666.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

Genes affected

PRORP-PSMA6 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRORP-PSMA6	NR_182666.1	n.3151+13649C>A		intron_variant, non_coding_transcript_variant
PSMA6	NM_002791.3			upstream_gene_variant		ENST00000261479.9	NP_002782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMA6	ENST00000261479.9			upstream_gene_variant		1	NM_002791.3	ENSP00000261479	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16366 AN: 152126 Hom.: 942 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.115 AC: 157914 AN: 1375622 Hom.: 9622 Cov.: 30 AF XY: 0.116 AC XY: 78364 AN XY: 677234

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0628

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.00139

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0790

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.107 AC: 16365 AN: 152244 Hom.: 940 Cov.: 33 AF XY: 0.105 AC XY: 7794 AN XY: 74442

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0460 Hom.: 44

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs2277460; hg19: chr14-35761573;