Genetic Variant APEH:p.Tyr284Tyr (chr3-49676792-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001640.4(APEH):c.852T>C(p.Tyr284Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,614,072 control chromosomes in the GnomAD database, including 69,211 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 0.27 ( 6246 hom., cov: 33)

Exomes 𝑓: 0.29 ( 62965 hom. )

Consequence

APEH
NM_001640.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

44 publications found

Variant links:

Genes affected

APEH (HGNC:586): (acylaminoacyl-peptide hydrolase) This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]

APEH links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-1.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APEH	NM_001640.4 link	c.852T>C	p.Tyr284Tyr	synonymous_variant	Exon 9 of 22	ENST00000296456.10	NP_001631.3	P13798

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APEH	ENST00000296456.10 link	c.852T>C	p.Tyr284Tyr	synonymous_variant	Exon 9 of 22	1	NM_001640.4	ENSP00000296456.5		P13798

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41764

AN:

152112

Hom.:

6242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.0459

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.265

AC:

66732

AN:

251442

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.0451

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.285

AC:

416806

AN:

1461842

Hom.:

62965

Cov.:

AF XY:

0.284

AC XY:

206601

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.251

AC:

8419

AN:

33478

American (AMR)

AF:

0.157

AC:

7034

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

11511

AN:

26136

East Asian (EAS)

AF:

0.0436

AC:

1730

AN:

39700

South Asian (SAS)

AF:

0.234

AC:

20152

AN:

86258

European-Finnish (FIN)

AF:

0.431

AC:

23032

AN:

53420

Middle Eastern (MID)

AF:

0.304

AC:

1752

AN:

5768

European-Non Finnish (NFE)

AF:

0.293

AC:

325786

AN:

1111966

Other (OTH)

AF:

0.288

AC:

17390

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20574

41148

61722

82296

102870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.275

AC:

41788

AN:

152230

Hom.:

6246

Cov.:

AF XY:

0.277

AC XY:

20583

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.251

AC:

10416

AN:

41538

American (AMR)

AF:

0.206

AC:

3159

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1535

AN:

3470

East Asian (EAS)

AF:

0.0460

AC:

238

AN:

5176

South Asian (SAS)

AF:

0.216

AC:

1043

AN:

4830

European-Finnish (FIN)

AF:

0.447

AC:

4739

AN:

10598

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19789

AN:

68004

Other (OTH)

AF:

0.284

AC:

601

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1562

3124

4687

6249

7811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.288

Hom.:

10491

Bravo

AF:

0.255

Asia WGS

AF:

0.131

AC:

461

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.23

(source)

DANN

Benign

0.42

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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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3-49676792-T-C

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