NM_002795.4:c.188+1238C>T

Variant names:

• chr17-38754572-C-T
• rs228275
• NM_002795.4:c.188+1238C>T

Variant summary

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

The NM_002795.4(PSMB3):​c.188+1238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,112 control chromosomes in the GnomAD database, including 8,702 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 0.32 (8702 hom., cov: 32)
• Consequence: PSMB3 NM_002795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 7 publications found

Genes affected

PSMB3 (HGNC:9540): (proteasome 20S subunit beta 3) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. The 26 S proteasome may be involved in trinucleotide repeat expansion, a phenomenon which is associated with many hereditary neurological diseases. Pseudogenes have been identified on chromosomes 2 and 12. Alternative splicing results in multiple transcript variants [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB3	NM_002795.4	c.188+1238C>T		intron_variant	Intron 2 of 5	ENST00000619426.5	NP_002786.2
PSMB3	NR_104194.2	n.274+1238C>T		intron_variant	Intron 2 of 4
PSMB3	NR_104195.2	n.274+1238C>T		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB3	ENST00000619426.5	c.188+1238C>T		intron_variant	Intron 2 of 5	1	NM_002795.4	ENSP00000483688.1
PSMB3	ENST00000610434.4	c.179+1238C>T		intron_variant	Intron 2 of 3	3		ENSP00000478737.1
PSMB3	ENST00000613870.4	n.188+1238C>T		intron_variant	Intron 2 of 5	3		ENSP00000481215.1
PSMB3	ENST00000620309.4	n.188+1238C>T		intron_variant	Intron 2 of 4	2		ENSP00000481442.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48733 AN: 151994 Hom.: 8705 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.321 AC: 48763 AN: 152112 Hom.: 8702 Cov.: 32 AF XY: 0.325 AC XY: 24170 AN XY: 74348

African (AFR) AF: 0.186 AC: 7719 AN: 41500

American (AMR) AF: 0.428 AC: 6543 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3357 AN: 5182

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4820

European-Finnish (FIN) AF: 0.345 AC: 3645 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23341 AN: 67970

Other (OTH) AF: 0.313 AC: 662 AN: 2114

Alfa AF: 0.341 Hom.: 38441

Bravo AF: 0.325

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.60
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: rs228275; hg19: chr17-36910825;