Genetic Variant PSMA4:c.-24+342A>C (chr15-78540881-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002789.6(PSMA4):c.-24+342A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 152,228 control chromosomes in the GnomAD database, including 67,664 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 0.94 ( 67625 hom., cov: 30)

Exomes 𝑓: 0.98 ( 39 hom. )

Consequence

PSMA4
NM_002789.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

16 publications found

Variant links:

Genes affected

PSMA4 (HGNC:9533): (proteasome 20S subunit alpha 4) This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]

PSMA4 links:

ENSG00000297479 (HGNC:):

ENSG00000297479 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002789.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PSMA4	NM_002789.6	MANE Select	c.-24+342A>C	intron	N/A	NP_002780.1	P25789-1
PSMA4	NM_001102667.2		c.-24+418A>C	intron	N/A	NP_001096137.1	P25789-1
PSMA4	NM_001330676.2		c.-24+46A>C	intron	N/A	NP_001317605.1	P25789-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PSMA4	ENST00000044462.12	TSL:1 MANE Select	c.-24+342A>C	intron	N/A	ENSP00000044462.7	P25789-1
PSMA4	ENST00000413382.6	TSL:1	c.-74+342A>C	intron	N/A	ENSP00000402118.2	P25789-2
PSMA4	ENST00000559934.5	TSL:1	n.438A>C	non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.940

AC:

142943

AN:

152028

Hom.:

67579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.974

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.980

Gnomad FIN

AF:

0.984

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.947

GnomAD4 exome

AF:

0.976

AC:

AN:

Hom.:

Cov.:

AF XY:

0.955

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.875

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.940

AC:

143045

AN:

152146

Hom.:

67625

Cov.:

AF XY:

0.942

AC XY:

70039

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.831

AC:

34435

AN:

41456

American (AMR)

AF:

0.976

AC:

14920

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.974

AC:

3380

AN:

3472

East Asian (EAS)

AF:

0.876

AC:

4522

AN:

5160

South Asian (SAS)

AF:

0.980

AC:

4720

AN:

4814

European-Finnish (FIN)

AF:

0.984

AC:

10449

AN:

10616

Middle Eastern (MID)

AF:

0.963

AC:

283

AN:

294

European-Non Finnish (NFE)

AF:

0.991

AC:

67424

AN:

68022

Other (OTH)

AF:

0.948

AC:

2002

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

401

801

1202

1602

2003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.973

Hom.:

280176

Bravo

AF:

0.933

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.0

(source)

DANN

Benign

0.67

PhyloP100

-0.066

PromoterAI

-0.070

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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