chr3-49682296-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001640.4(APEH):​c.1604-52G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,363,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

APEH
NM_001640.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930

Publications

59 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APEHNM_001640.4 linkc.1604-52G>C intron_variant Intron 17 of 21 ENST00000296456.10 NP_001631.3 P13798

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APEHENST00000296456.10 linkc.1604-52G>C intron_variant Intron 17 of 21 1 NM_001640.4 ENSP00000296456.5 P13798
APEHENST00000438011.5 linkc.1604-52G>C intron_variant Intron 17 of 21 1 ENSP00000415862.1 C9JIF9
APEHENST00000469362.6 linkn.*304-52G>C intron_variant Intron 6 of 8 3 ENSP00000438180.1 H0YFE5

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.34e-7
AC:
1
AN:
1363278
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
679486
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31040
American (AMR)
AF:
0.00
AC:
0
AN:
41086
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25304
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37556
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82052
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51924
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5592
European-Non Finnish (NFE)
AF:
9.69e-7
AC:
1
AN:
1031858
Other (OTH)
AF:
0.00
AC:
0
AN:
56866
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
34
Alfa
AF:
0.00
Hom.:
16712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.9
DANN
Benign
0.65
PhyloP100
0.093
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs9822268; hg19: chr3-49719729; API