rs10199752

Positions:

• chr2-231104840-A-C
• chr2-231104840-A-G

Variant summary

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

The ENST00000308696.11(PSMD1):​c.1883+17659A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,988 control chromosomes in the GnomAD database, including 21,823 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 0.49 (21823 hom., cov: 32)
• Consequence: PSMD1 ENST00000308696.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

Genes affected

PSMD1 (HGNC:9554): (proteasome 26S subunit, non-ATPase 1) 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 the largest non-ATPase subunit of the 19S regulator lid, which is responsible for substrate recognition and binding. There is evidence that this proteasome and its subunits interact with viral proteins, including those of coronaviruses. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMD1	NM_002807.4	c.1883+17659A>C		intron_variant		ENST00000308696.11	NP_002798.2
PSMD1	NM_001191037.2	c.1883+17659A>C		intron_variant			NP_001177966.1
PSMD1	NR_034059.2	n.1872+17659A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMD1	ENST00000308696.11	c.1883+17659A>C		intron_variant		1	NM_002807.4	ENSP00000309474	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74626 AN: 151870 Hom.: 21772 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.492 AC: 74732 AN: 151988 Hom.: 21823 Cov.: 32 AF XY: 0.494 AC XY: 36699 AN XY: 74292

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.461

Alfa AF: 0.345 Hom.: 9414

Bravo AF: 0.498

Asia WGS AF: 0.582 AC: 2022 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.63

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: rs10199752; hg19: chr2-231969554;