3-49676792-T-C

Variant names:

• chr3-49676792-T-C
• rs1131095
• NM_001640.4:c.852T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 44 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001640.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APEH	NM_001640.4	MANE Select	c.852T>C	p.Tyr284Tyr	synonymous	Exon 9 of 22	NP_001631.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APEH	ENST00000296456.10	TSL:1 MANE Select	c.852T>C	p.Tyr284Tyr	synonymous	Exon 9 of 22	ENSP00000296456.5
	APEH	ENST00000438011.5	TSL:1	c.852T>C	p.Tyr284Tyr	synonymous	Exon 9 of 22	ENSP00000415862.1
	APEH	ENST00000442186.5	TSL:5	c.627T>C	p.Tyr209Tyr	synonymous	Exon 7 of 10	ENSP00000402365.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41764 AN: 152112 Hom.: 6242 Cov.: 33

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

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.: 64 AF XY: 0.284 AC XY: 206601 AN XY: 727240

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

GnomAD4 genome AF: 0.275 AC: 41788 AN: 152230 Hom.: 6246 Cov.: 33 AF XY: 0.277 AC XY: 20583 AN XY: 74408

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: 90 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19789 AN: 68004

Other (OTH) AF: 0.284 AC: 601 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.23
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)

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

Other links and lift over

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