dbSNP rs2348071: PSMA3:c.543+138A>G (chr14-58263908-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002788.4(PSMA3):c.543+138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 674,790 control chromosomes in the GnomAD database, including 167,452 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 0.70 ( 37955 hom., cov: 32)

Exomes 𝑓: 0.70 ( 129497 hom. )

Consequence

PSMA3
NM_002788.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0390

Publications

19 publications found

Variant links:

Genes affected

PSMA3 (HGNC:9532): (proteasome 20S subunit alpha 3) 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. Two alternative transcripts encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PSMA3 links:

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARMH4 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002788.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PSMA3	NM_002788.4	MANE Select	c.543+138A>G	intron	N/A	NP_002779.1	A0A140VK43
PSMA3	NM_152132.3		c.522+138A>G	intron	N/A	NP_687033.1	P25788-2
PSMA3	NR_038123.2		n.538+138A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PSMA3	ENST00000216455.9	TSL:1 MANE Select	c.543+138A>G	intron	N/A	ENSP00000216455.4	P25788-1
PSMA3	ENST00000412908.6	TSL:1	c.522+138A>G	intron	N/A	ENSP00000390491.2	P25788-2
PSMA3	ENST00000925587.1		c.543+138A>G	intron	N/A	ENSP00000595646.1

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106831

AN:

151908

Hom.:

37942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.908

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.406

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.731

GnomAD4 exome

AF:

0.696

AC:

363809

AN:

522764

Hom.:

129497

AF XY:

0.698

AC XY:

193082

AN XY:

276534

show subpopulations

African (AFR)

AF:

0.723

AC:

9775

AN:

13522

American (AMR)

AF:

0.665

AC:

14254

AN:

21432

Ashkenazi Jewish (ASJ)

AF:

0.812

AC:

12370

AN:

15230

East Asian (EAS)

AF:

0.385

AC:

12148

AN:

31558

South Asian (SAS)

AF:

0.705

AC:

35218

AN:

49972

European-Finnish (FIN)

AF:

0.631

AC:

28753

AN:

45540

Middle Eastern (MID)

AF:

0.841

AC:

2387

AN:

2838

European-Non Finnish (NFE)

AF:

0.728

AC:

229226

AN:

314952

Other (OTH)

AF:

0.710

AC:

19678

AN:

27720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4986

9971

14957

19942

24928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1864

3728

5592

7456

9320

<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:

0.703

AC:

106886

AN:

152026

Hom.:

37955

Cov.:

AF XY:

0.699

AC XY:

51933

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.713

AC:

29595

AN:

41498

American (AMR)

AF:

0.700

AC:

10686

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

2850

AN:

3472

East Asian (EAS)

AF:

0.407

AC:

2098

AN:

5158

South Asian (SAS)

AF:

0.685

AC:

3301

AN:

4816

European-Finnish (FIN)

AF:

0.629

AC:

6634

AN:

10542

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.723

AC:

49122

AN:

67962

Other (OTH)

AF:

0.721

AC:

1518

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1565

3131

4696

6262

7827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.709

Hom.:

4923

Bravo

AF:

0.710

Asia WGS

AF:

0.533

AC:

1851

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.3

(source)

DANN

Benign

0.33

PhyloP100

0.039

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over