3-51984112-C-T

Variant names:

• chr3-51984112-C-T
• rs200012512
• NM_000666.3:c.48C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP4_Moderate BP6_Moderate BP7 BS1

The NM_000666.3(ACY1):​c.48C>T​(p.Phe16Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ACY1 NM_000666.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

Genes affected

ACY1 (HGNC:177): (aminoacylase 1) This gene encodes a cytosolic, homodimeric, zinc-binding enzyme that catalyzes the hydrolysis of acylated L-amino acids to L-amino acids and an acyl group, and has been postulated to function in the catabolism and salvage of acylated amino acids. This gene is located on chromosome 3p21.1, a region reduced to homozygosity in small-cell lung cancer (SCLC), and its expression has been reported to be reduced or undetectable in SCLC cell lines and tumors. The amino acid sequence of human aminoacylase-1 is highly homologous to the porcine counterpart, and this enzyme is the first member of a new family of zinc-binding enzymes. Mutations in this gene cause aminoacylase-1 deficiency, a metabolic disorder characterized by central nervous system defects and increased urinary excretion of N-acetylated amino acids. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ABHD14A (abhydrolase domain containing 14A) gene, as represented in GeneID:100526760. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Nov 2010]

ABHD14A-ACY1 (HGNC:38856): (ABHD14A-ACY1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring abhydrolase domain containing 14A (ABHD14A) and aminoacylase 1 (ACY1) genes on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the downstream gene product but its N-terminal region is distinct due to the use of an alternate start codon relative to the upstream gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 3-51984112-C-T is Benign according to our data. Variant chr3-51984112-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 731084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.92 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000499 (76/152356) while in subpopulation AFR AF= 0.0018 (75/41582). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACY1	NM_000666.3	c.48C>T	p.Phe16Phe	synonymous_variant	Exon 2 of 15	ENST00000636358.2	NP_000657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACY1	ENST00000636358.2	c.48C>T	p.Phe16Phe	synonymous_variant	Exon 2 of 15	1	NM_000666.3	ENSP00000490149.1
ABHD14A-ACY1	ENST00000463937.1	c.398-1095C>T		intron_variant	Intron 3 of 15	5		ENSP00000420487.1

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000108 AC: 27 AN: 250688 Hom.: 0 AF XY: 0.000103 AC XY: 14 AN XY: 135652

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461572 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727074

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34 AN XY: 74498

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000252 Hom.: 0

Bravo AF: 0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs200012512; hg19: chr3-52018128;