chr14-35292469-C-G

Variant names:

• chr14-35292469-C-G
• rs1048990
• NM_002791.3:c.-8C>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002791.3(PSMA6):​c.-8C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,878 control chromosomes in the GnomAD database, including 26,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (2134 hom., cov: 33)
  • Exomes 𝑓: 0.18 (23956 hom.)
• Consequence: PSMA6 NM_002791.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign; risk factor no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: -0.965

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 14-35292469-C-G is Benign according to our data. Variant chr14-35292469-C-G is described in ClinVar as [Benign, risk_factor]. Clinvar id is 6796.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA6	NM_002791.3	c.-8C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000261479.9	NP_002782.1
PSMA6	NM_002791.3	c.-8C>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000261479.9	NP_002782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMA6	ENST00000261479	c.-8C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_002791.3	ENSP00000261479.4
PSMA6	ENST00000261479	c.-8C>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_002791.3	ENSP00000261479.4
ENSG00000258790	ENST00000557565.1	n.*891+13751C>G		intron_variant	Intron 9 of 14	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22916 AN: 152146 Hom.: 2133 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.188 AC: 47053 AN: 250420 Hom.: 5020 AF XY: 0.190 AC XY: 25737 AN XY: 135402

Gnomad AFR exome AF: 0.0554

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.175 AC: 255623 AN: 1460614 Hom.: 23956 Cov.: 33 AF XY: 0.176 AC XY: 128235 AN XY: 726638

Gnomad4 AFR exome AF: 0.0510

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.151 AC: 22921 AN: 152264 Hom.: 2134 Cov.: 33 AF XY: 0.153 AC XY: 11400 AN XY: 74438

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.167

Alfa AF: 0.145 Hom.: 611

Bravo AF: 0.150

Asia WGS AF: 0.298 AC: 1033 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.171

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

PSMA6-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Myocardial infarction, susceptibility to Other:1

Apr 01, 2009

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.61
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1048990; hg19: chr14-35761675; COSMIC: COSV54836961; COSMIC: COSV54836961;