Genetic Variant ENSG00000258790:n.*891+13649C>T (chr14-35292367-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000557565.1(ENSG00000258790):n.*891+13649C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,528,254 control chromosomes in the GnomAD database, including 23 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 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 23 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:

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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=-0.75).

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000946 (1302/1375990) while in subpopulation EAS AF = 0.0281 (1052/37386). AF 95% confidence interval is 0.0267. There are 23 homozygotes in GnomAdExome4. There are 623 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMA6	NM_002791.3 link	c.-110C>T		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>T		intron_variant	Intron 9 of 14	2		ENSP00000454657.1
PSMA6	ENST00000261479.9 link	c.-110C>T		upstream_gene_variant		1	NM_002791.3	ENSP00000261479.4		P60900-1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000946

AC:

1302

AN:

1375990

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

623

AN XY:

677426

show subpopulations

African (AFR)

AF:

0.0000330

AC:

AN:

30330

American (AMR)

AF:

0.00177

AC:

AN:

32772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20724

East Asian (EAS)

AF:

0.0281

AC:

1052

AN:

37386

South Asian (SAS)

AF:

0.000407

AC:

AN:

73762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3730

European-Non Finnish (NFE)

AF:

0.000107

AC:

115

AN:

1070702

Other (OTH)

AF:

0.000815

AC:

AN:

56448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000657

AC:

100

AN:

152264

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.000458

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0158

AC:

AN:

5174

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.010

PromoterAI

-0.037

Neutral

(source)

Mutation Taster

=100/0

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

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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