rs17336700

chr16-74301306-T-Cchr16-74301306-T-G

Variant summary

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

The NM_002811.5(PSMD7):c.259+162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,966 control chromosomes in the GnomAD database, including 1,430 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 0.12 (1430 hom., cov: 32)
• Consequence: PSMD7 NM_002811.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

Genes affected

PSMD7 (HGNC:9565): (proteasome 26S subunit, non-ATPase 7) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD7	NM_002811.5	c.259+162T>C		intron_variant		ENST00000219313.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD7	ENST00000219313.9	c.259+162T>C		intron_variant		1	NM_002811.5	P1
PSMD7	ENST00000567958.5	c.259+162T>C		intron_variant		3
PSMD7	ENST00000568615.2	c.259+162T>C		intron_variant		2
PSMD7	ENST00000568717.1	c.*297+162T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17852 AN: 151848 Hom.: 1429 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.117 AC: 17853 AN: 151966 Hom.: 1430 Cov.: 32 AF XY: 0.122 AC XY: 9090 AN XY: 74276

Gnomad4 AFR AF: 0.0282

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.108

Alfa AF: 0.128 Hom.: 779

Bravo AF: 0.117

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.0
Dann	Benign	0.62

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: rs17336700; hg19: chr16-74335204;