11-14507704-C-T

Variant names:

• chr11-14507704-C-T
• rs61732660
• NM_002786.4:c.687G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_002786.4(PSMA1):​c.687G>A​(p.Val229Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,034 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (22 hom.)
• Consequence: PSMA1 NM_002786.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26
• Publications: 1 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-14507704-C-T is Benign according to our data. Variant chr11-14507704-C-T is described in ClinVar as Benign. ClinVar VariationId is 716419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.26 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00871 (1324/152060) while in subpopulation AFR AF = 0.0305 (1265/41460). AF 95% confidence interval is 0.0291. There are 16 homozygotes in GnomAd4. There are 662 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1324 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.687G>A	p.Val229Val	synonymous	Exon 9 of 10	NP_002777.1	P25786-1
	PSMA1	NM_148976.3		c.705G>A	p.Val235Val	synonymous	Exon 10 of 11	NP_683877.1	P25786-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMA1	ENST00000396394.7	TSL:1 MANE Select	c.687G>A	p.Val229Val	synonymous	Exon 9 of 10	ENSP00000379676.2	P25786-1
	PSMA1	ENST00000418988.2	TSL:1	c.705G>A	p.Val235Val	synonymous	Exon 10 of 11	ENSP00000414359.2	P25786-2
	ENSG00000256206	ENST00000555531.1	TSL:2	n.*134G>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000457299.1	B4DEV8

Frequencies

GnomAD3 genomes AF: 0.00868 AC: 1319 AN: 151942 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00215 AC: 539 AN: 251214 AF XY: 0.00158

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000835 AC: 1220 AN: 1460974 Hom.: 22 Cov.: 30 AF XY: 0.000728 AC XY: 529 AN XY: 726844

African (AFR) AF: 0.0298 AC: 997 AN: 33410

American (AMR) AF: 0.00170 AC: 76 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5760

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111370

Other (OTH) AF: 0.00161 AC: 97 AN: 60362

GnomAD4 genome AF: 0.00871 AC: 1324 AN: 152060 Hom.: 16 Cov.: 32 AF XY: 0.00891 AC XY: 662 AN XY: 74332

African (AFR) AF: 0.0305 AC: 1265 AN: 41460

American (AMR) AF: 0.00288 AC: 44 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67986

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00416 Hom.: 8

Bravo AF: 0.00978

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism

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: rs61732660; hg19: chr11-14529250;