14-35286531-C-T

Variant names:

• chr14-35286531-C-T
• rs4982254
• ENST00000557565.1:n.*891+7813C>T

Variant summary

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

The NM_001282234.1(PSMA6):​c.19+7813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,876 control chromosomes in the GnomAD database, including 3,128 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 0.19 (3128 hom., cov: 32)
• Consequence: PSMA6 NM_001282234.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282234.1. 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_001282234.1		c.19+7813C>T		intron	N/A	NP_001269163.1	P60900-2
	PRORP-PSMA6	NR_182666.1		n.3151+7813C>T		intron	N/A
	PRORP-PSMA6	NR_182667.1		n.2973+7813C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000258790	ENST00000557565.1	TSL:2	n.*891+7813C>T		intron	N/A	ENSP00000454657.1
	PSMA6	ENST00000540871.5	TSL:2	c.19+7813C>T		intron	N/A	ENSP00000444844.1	P60900-2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28236 AN: 151758 Hom.: 3127 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.0595

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.186 AC: 28250 AN: 151876 Hom.: 3128 Cov.: 32 AF XY: 0.191 AC XY: 14139 AN XY: 74196

African (AFR) AF: 0.0642 AC: 2659 AN: 41416

American (AMR) AF: 0.162 AC: 2467 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1688 AN: 5178

South Asian (SAS) AF: 0.205 AC: 985 AN: 4816

European-Finnish (FIN) AF: 0.289 AC: 3033 AN: 10508

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16409 AN: 67928

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.216 Hom.: 2172

Bravo AF: 0.170

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.21
DANN	Benign	0.73
PhyloP100		-0.12
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: rs4982254; hg19: chr14-35755737;