NM_002800.5:c.60+203A>C

Variant names:

• chr6-32854492-A-C
• rs1351383
• NM_002800.5:c.60+203A>C

Variant summary

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

The NM_002800.5(PSMB9):​c.60+203A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,924 control chromosomes in the GnomAD database, including 13,996 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 0.43 (13996 hom., cov: 31)
• Consequence: PSMB9 NM_002800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) 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. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB9	NM_002800.5	c.60+203A>C		intron_variant	Intron 1 of 5	ENST00000374859.3	NP_002791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB9	ENST00000374859.3	c.60+203A>C		intron_variant	Intron 1 of 5	1	NM_002800.5	ENSP00000363993.2
PSMB9	ENST00000395330.5	c.-9-1646A>C		intron_variant	Intron 1 of 5	3		ENSP00000378739.1
PSMB9	ENST00000414474.5	c.-9-1646A>C		intron_variant	Intron 1 of 4	5		ENSP00000394363.1
PSMB9	ENST00000464863.1	n.142+203A>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64774 AN: 151806 Hom.: 13974 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.427 AC: 64842 AN: 151924 Hom.: 13996 Cov.: 31 AF XY: 0.423 AC XY: 31408 AN XY: 74242

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.433

Alfa AF: 0.424 Hom.: 14454

Bravo AF: 0.430

Asia WGS AF: 0.451 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.37

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: rs1351383; hg19: chr6-32822269;