14-35292367-C-G

Variant names:

• chr14-35292367-C-G
• rs2277460
• ENST00000557565.1:n.*891+13649C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282232.1(PSMA6):​c.-395C>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 0.000000727 in 1,375,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PSMA6 NM_001282232.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 0 publications found

Genes affected

ENSG00000258790 (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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282232.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA6	NM_001282232.1		c.-395C>G		5_prime_UTR	Exon 1 of 7	NP_001269161.1	P60900-3
	PSMA6	NM_001282233.1		c.-252C>G		5_prime_UTR	Exon 1 of 6	NP_001269162.1	P60900-3
	PSMA6	NM_001282234.1		c.19+13649C>G		intron	N/A	NP_001269163.1	P60900-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000258790	ENST00000557565.1	TSL:2	n.*891+13649C>G		intron	N/A	ENSP00000454657.1
	PSMA6	ENST00000929332.1		c.-110C>G		5_prime_UTR	Exon 1 of 7	ENSP00000599391.1
	PSMA6	ENST00000929333.1		c.-110C>G		5_prime_UTR	Exon 1 of 7	ENSP00000599392.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375994 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 677428

African (AFR) AF: 0.00 AC: 0 AN: 30330

American (AMR) AF: 0.00 AC: 0 AN: 32772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20724

East Asian (EAS) AF: 0.00 AC: 0 AN: 37390

South Asian (SAS) AF: 0.00 AC: 0 AN: 73762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070702

Other (OTH) AF: 0.0000177 AC: 1 AN: 56448

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		-0.010
PromoterAI		0.0051	Neutral

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: rs2277460; hg19: chr14-35761573;