rs1131095

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000296456.10(APEH):ā€‹c.852T>Cā€‹(p.Tyr284=) 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: š‘“ 0.27 ( 6246 hom., cov: 33)
Exomes š‘“: 0.29 ( 62965 hom. )

Consequence

APEH
ENST00000296456.10 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
APEHNM_001640.4 linkuse as main transcriptc.852T>C p.Tyr284= synonymous_variant 9/22 ENST00000296456.10 NP_001631.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APEHENST00000296456.10 linkuse as main transcriptc.852T>C p.Tyr284= synonymous_variant 9/221 NM_001640.4 ENSP00000296456 P1

Frequencies

GnomAD3 genomes
AF:
0.275
AC:
41764
AN:
152112
Hom.:
6242
Cov.:
33
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
GnomAD3 exomes
AF:
0.265
AC:
66732
AN:
251442
Hom.:
10363
AF XY:
0.269
AC XY:
36503
AN XY:
135894
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 SAS exome
AF:
0.228
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.:
64
AF XY:
0.284
AC XY:
206601
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.251
Gnomad4 AMR exome
AF:
0.157
Gnomad4 ASJ exome
AF:
0.440
Gnomad4 EAS exome
AF:
0.0436
Gnomad4 SAS exome
AF:
0.234
Gnomad4 FIN exome
AF:
0.431
Gnomad4 NFE exome
AF:
0.293
Gnomad4 OTH exome
AF:
0.288
GnomAD4 genome
AF:
0.275
AC:
41788
AN:
152230
Hom.:
6246
Cov.:
33
AF XY:
0.277
AC XY:
20583
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.251
Gnomad4 AMR
AF:
0.206
Gnomad4 ASJ
AF:
0.442
Gnomad4 EAS
AF:
0.0460
Gnomad4 SAS
AF:
0.216
Gnomad4 FIN
AF:
0.447
Gnomad4 NFE
AF:
0.291
Gnomad4 OTH
AF:
0.284
Alfa
AF:
0.292
Hom.:
8716
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
DANN
Benign
0.42
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1131095; hg19: chr3-49714225; COSMIC: COSV56532048; COSMIC: COSV56532048; API