11-252231-C-T

Variant names:

• chr11-252231-C-T
• rs3817630
• NM_002817.4:c.1036-274C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002817.4(PSMD13):​c.1036-274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSMD13 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

Genes affected

PSMD13 (HGNC:9558): (proteasome 26S subunit, non-ATPase 13) 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. Two transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.1036-274C>T		intron_variant	Intron 12 of 12	ENST00000532097.6	NP_002808.3
PSMD13	NM_175932.3	c.1042-274C>T		intron_variant	Intron 10 of 10		NP_787128.2
PSMD13	XM_011520235.4	c.838-274C>T		intron_variant	Intron 10 of 10		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6	c.1036-274C>T		intron_variant	Intron 12 of 12	1	NM_002817.4	ENSP00000436186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 361354 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 188988

African (AFR) AF: 0.00 AC: 0 AN: 11028

American (AMR) AF: 0.00 AC: 0 AN: 15386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11582

East Asian (EAS) AF: 0.00 AC: 0 AN: 25474

South Asian (SAS) AF: 0.00 AC: 0 AN: 36392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 216486

Other (OTH) AF: 0.00 AC: 0 AN: 21406

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		1.0

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: rs3817630; hg19: chr11-252231;