chr11-237312-T-C

Variant names:

• chr11-237312-T-C
• rs3817629
• NM_002817.4:c.95+168T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002817.4(PSMD13):​c.95+168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,124 control chromosomes in the GnomAD database, including 48,178 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 0.79 (48178 hom., cov: 32)
• Consequence: PSMD13 NM_002817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMD13	NM_002817.4	c.95+168T>C		intron_variant	Intron 1 of 12	ENST00000532097.6	NP_002808.3
PSMD13	NM_175932.3	c.95+168T>C		intron_variant	Intron 1 of 10		NP_787128.2
PSMD13	XM_011520235.4	c.95+168T>C		intron_variant	Intron 1 of 10		XP_011518537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMD13	ENST00000532097.6	c.95+168T>C		intron_variant	Intron 1 of 12	1	NM_002817.4	ENSP00000436186.1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120590 AN: 152006 Hom.: 48127 Cov.: 32

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.793 AC: 120693 AN: 152124 Hom.: 48178 Cov.: 32 AF XY: 0.796 AC XY: 59189 AN XY: 74354

African (AFR) AF: 0.884 AC: 36712 AN: 41532

American (AMR) AF: 0.808 AC: 12352 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2388 AN: 3466

East Asian (EAS) AF: 0.827 AC: 4273 AN: 5166

South Asian (SAS) AF: 0.795 AC: 3832 AN: 4820

European-Finnish (FIN) AF: 0.766 AC: 8092 AN: 10570

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50592 AN: 67964

Other (OTH) AF: 0.756 AC: 1596 AN: 2112

Alfa AF: 0.731 Hom.: 2743

Bravo AF: 0.802

Asia WGS AF: 0.804 AC: 2798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.46
PhyloP100		-0.49
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3817629; hg19: chr11-237312; COSMIC: COSV61500565; COSMIC: COSV61500565;