rs757557606

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002791.3(PSMA6):c.547G>A(p.Val183Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,579,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

PSMA6
NM_002791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Publications

0 publications found

Variant links:

Genes affected

PSMA6 (HGNC:9535): (proteasome 20S subunit alpha 6) 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. Multiple transcript variants encoding several different isoforms have been found for this gene. A pseudogene has been identified on the Y chromosome. [provided by RefSeq, Aug 2013]

PSMA6 links:

ENSG00000258790 (HGNC:):

ENSG00000258790 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.179647).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMA6	NM_002791.3	MANE Select	c.547G>A	p.Val183Met	missense	Exon 5 of 7	NP_002782.1	P60900-1
PSMA6	NM_001282234.1		c.490G>A	p.Val164Met	missense	Exon 5 of 7	NP_001269163.1	P60900-2
PSMA6	NM_001282232.1		c.310G>A	p.Val104Met	missense	Exon 5 of 7	NP_001269161.1	P60900-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMA6	ENST00000261479.9	TSL:1 MANE Select	c.547G>A	p.Val183Met	missense	Exon 5 of 7	ENSP00000261479.4	P60900-1
ENSG00000258790	ENST00000557565.1	TSL:2	n.*1362G>A		non_coding_transcript_exon	Exon 13 of 15	ENSP00000454657.1
ENSG00000258790	ENST00000557565.1	TSL:2	n.*1362G>A		3_prime_UTR	Exon 13 of 15	ENSP00000454657.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000139

AC:

AN:

215492

AF XY:

0.00000850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000291

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000841

AC:

AN:

1427322

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

710202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30478

American (AMR)

AF:

0.00

AC:

AN:

33094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24836

East Asian (EAS)

AF:

0.00

AC:

AN:

38376

South Asian (SAS)

AF:

0.00

AC:

AN:

80212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.00000907

AC:

AN:

1102520

Other (OTH)

AF:

0.0000339

AC:

AN:

58990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74282

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41402

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.085

Eigen

Benign

-0.0073

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.0094

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.93

PhyloP100

4.8

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.45

REVEL

Benign

0.15

Sift

Benign

0.41

Sift4G

Benign

0.28

Polyphen

0.011

Vest4

0.44

MutPred

0.52

Loss of methylation at K182 (P = 0.0185)

MVP

0.40

MPC

0.65

ClinPred

0.25

GERP RS

5.6

Varity_R

0.20

gMVP

0.76

Mutation Taster

=58/42

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over