rs552770453

Variant names:

• chr11-14519042-CTAAAAG-C
• rs552770453
• NM_002786.4:c.4-7_4-2delCTTTTA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PVS1_Moderate BP6_Moderate BS2

The NM_002786.4(PSMA1):​c.4-7_4-2delCTTTTA variant causes a splice acceptor, splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,581,644 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (3 hom.)
• Consequence: PSMA1 NM_002786.4 splice_acceptor, splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.25
• Publications: 0 publications found

Genes affected

PSMA1 (HGNC:9530): (proteasome 20S subunit alpha 1) 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 peptidase T1A family, that is a 20S core alpha subunit. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]

ENSG00000256206 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.056818184 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.5, offset of 0 (no position change), new splice context is: caggtatttttttcttttAGttt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BP6: Variant 11-14519042-CTAAAAG-C is Benign according to our data. Variant chr11-14519042-CTAAAAG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 784186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 392 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA1	NM_002786.4	MANE Select	c.4-7_4-2delCTTTTA		splice_acceptor splice_region intron	N/A	NP_002777.1	P25786-1
	PSMA1	NM_148976.3		c.22-7_22-2delCTTTTA		splice_acceptor splice_region intron	N/A	NP_683877.1	P25786-2
	PSMA1	NM_001143937.2		c.4-7_4-2delCTTTTA		splice_acceptor splice_region intron	N/A	NP_001137409.1	B4E0X6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA1	ENST00000396394.7	TSL:1 MANE Select	c.4-7_4-2delCTTTTA		splice_acceptor splice_region intron	N/A	ENSP00000379676.2	P25786-1
	PSMA1	ENST00000418988.2	TSL:1	c.22-7_22-2delCTTTTA		splice_acceptor splice_region intron	N/A	ENSP00000414359.2	P25786-2
	ENSG00000256206	ENST00000555531.1	TSL:2	n.4-7_4-2delCTTTTA		splice_acceptor splice_region intron	N/A	ENSP00000457299.1	B4DEV8

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 394 AN: 152142 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000895 AC: 214 AN: 239200 AF XY: 0.000687

Gnomad AFR exome AF: 0.00904

Gnomad AMR exome AF: 0.000511

Gnomad ASJ exome AF: 0.00491

Gnomad EAS exome AF: 0.0000567

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000634

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.000337 AC: 481 AN: 1429384 Hom.: 3 AF XY: 0.000316 AC XY: 225 AN XY: 712108

African (AFR) AF: 0.00721 AC: 231 AN: 32018

American (AMR) AF: 0.000633 AC: 26 AN: 41104

Ashkenazi Jewish (ASJ) AF: 0.00534 AC: 136 AN: 25478

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39434

South Asian (SAS) AF: 0.0000362 AC: 3 AN: 82862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.000530 AC: 3 AN: 5662

European-Non Finnish (NFE) AF: 0.0000275 AC: 30 AN: 1090356

Other (OTH) AF: 0.000861 AC: 51 AN: 59226

GnomAD4 genome AF: 0.00257 AC: 392 AN: 152260 Hom.: 2 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74450

African (AFR) AF: 0.00859 AC: 357 AN: 41550

American (AMR) AF: 0.000654 AC: 10 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00190 Hom.: 0

Bravo AF: 0.00267

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2
Mutation Taster		=98/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs552770453; hg19: chr11-14540588;