rs7212835

chr17-32471507-A-G

Variant summary

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

The NM_002815.4(PSMD11):c.644-2294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,254 control chromosomes in the GnomAD database, including 2,591 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 0.17 (2591 hom., cov: 32)
• Consequence: PSMD11 NM_002815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

Genes affected

PSMD11 (HGNC:9556): (proteasome 26S subunit, non-ATPase 11) 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. This gene encodes a member of the proteasome subunit S9 family that functions as a non-ATPase subunit of the 19S regulator and is phosphorylated by AMP-activated protein kinase. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMD11	NM_002815.4	c.644-2294A>G		intron_variant		ENST00000261712.8
PSMD11	NM_001270482.2	c.644-2294A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMD11	ENST00000261712.8	c.644-2294A>G		intron_variant		1	NM_002815.4	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25139 AN: 152136 Hom.: 2590 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.165 AC: 25173 AN: 152254 Hom.: 2591 Cov.: 32 AF XY: 0.163 AC XY: 12120 AN XY: 74454

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0484

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.151

Alfa AF: 0.140 Hom.: 909

Bravo AF: 0.169

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.042
Dann	Benign	0.44

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: rs7212835; hg19: chr17-30798525;