dbSNP rs2277460: ENSG00000258790:n.*891+13649C>A (chr14-35292367-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000557565.1(ENSG00000258790):n.*891+13649C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,527,866 control chromosomes in the GnomAD database, including 10,562 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 0.11 ( 940 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9622 hom. )

Consequence

ENSG00000258790
ENST00000557565.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

17 publications found

Variant links:

Genes affected

ENSG00000258790 (HGNC:):

ENSG00000258790 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA6	NM_002791.3 link	c.-110C>A		upstream_gene_variant		ENST00000261479.9	NP_002782.1	P60900-1A0A140VK44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258790	ENST00000557565.1 link	n.*891+13649C>A		intron_variant	Intron 9 of 14	2		ENSP00000454657.1
PSMA6	ENST00000261479.9 link	c.-110C>A		upstream_gene_variant		1	NM_002791.3	ENSP00000261479.4		P60900-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16366

AN:

152126

Hom.:

942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0796

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.115

AC:

157914

AN:

1375622

Hom.:

9622

Cov.:

AF XY:

0.116

AC XY:

78364

AN XY:

677234

show subpopulations

African (AFR)

AF:

0.118

AC:

3585

AN:

30306

American (AMR)

AF:

0.0628

AC:

2055

AN:

32744

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2161

AN:

20706

East Asian (EAS)

AF:

0.00139

AC:

AN:

37390

South Asian (SAS)

AF:

0.141

AC:

10402

AN:

73726

European-Finnish (FIN)

AF:

0.0790

AC:

3961

AN:

50118

Middle Eastern (MID)

AF:

0.156

AC:

583

AN:

3728

European-Non Finnish (NFE)

AF:

0.120

AC:

128940

AN:

1070472

Other (OTH)

AF:

0.109

AC:

6175

AN:

56432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6727

13455

20182

26910

33637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4788

9576

14364

19152

23940

<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:

0.107

AC:

16365

AN:

152244

Hom.:

940

Cov.:

AF XY:

0.105

AC XY:

7794

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.115

AC:

4794

AN:

41554

American (AMR)

AF:

0.0795

AC:

1215

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

366

AN:

3470

East Asian (EAS)

AF:

0.00213

AC:

AN:

5176

South Asian (SAS)

AF:

0.138

AC:

667

AN:

4822

European-Finnish (FIN)

AF:

0.0774

AC:

821

AN:

10608

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8159

AN:

68010

Other (OTH)

AF:

0.102

AC:

216

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

755

1510

2266

3021

3776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0492

Hom.:

Bravo

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

-0.010

PromoterAI

0.0039

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over