rs7212835

Variant names:

• chr17-32471507-A-G
• rs7212835
• NM_002815.4:c.644-2294A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

PSMD11 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSMD11	NM_002815.4	c.644-2294A>G		intron_variant	Intron 6 of 13	ENST00000261712.8	NP_002806.2
PSMD11	NM_001270482.2	c.644-2294A>G		intron_variant	Intron 6 of 12		NP_001257411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD11	ENST00000261712.8	c.644-2294A>G		intron_variant	Intron 6 of 13	1	NM_002815.4	ENSP00000261712.3

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

African (AFR) AF: 0.279 AC: 11599 AN: 41510

American (AMR) AF: 0.118 AC: 1810 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.0484 AC: 251 AN: 5186

South Asian (SAS) AF: 0.183 AC: 882 AN: 4820

European-Finnish (FIN) AF: 0.0917 AC: 974 AN: 10624

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8774 AN: 68026

Other (OTH) AF: 0.151 AC: 318 AN: 2110

Alfa AF: 0.140 Hom.: 1024

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
PhyloP100		-0.69
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: rs7212835; hg19: chr17-30798525;