chr3-51986588-C-A

Position:

• chr3-51986588-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000666.3(ACY1):​c.527-17C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,614,130 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (175 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (169 hom.)
• Consequence: ACY1 NM_000666.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00300

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 3-51986588-C-A is Benign according to our data. Variant chr3-51986588-C-A is described in ClinVar as [Benign]. Clinvar id is 256755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACY1	NM_000666.3	c.527-17C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000636358.2	NP_000657.1
ABHD14A-ACY1	NM_001316331.2	c.797-17C>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001303260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACY1	ENST00000636358.2	c.527-17C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000666.3	ENSP00000490149	P1

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3964 AN: 152172 Hom.: 172 Cov.: 33

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.00741 AC: 1864 AN: 251434 Hom.: 85 AF XY: 0.00558 AC XY: 759 AN XY: 135900

Gnomad AFR exome AF: 0.0905

Gnomad AMR exome AF: 0.00723

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00323 AC: 4727 AN: 1461840 Hom.: 169 Cov.: 33 AF XY: 0.00290 AC XY: 2110 AN XY: 727226

Gnomad4 AFR exome AF: 0.0885

Gnomad4 AMR exome AF: 0.00796

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000703

Gnomad4 OTH exome AF: 0.00816

GnomAD4 genome AF: 0.0262 AC: 3986 AN: 152290 Hom.: 175 Cov.: 33 AF XY: 0.0245 AC XY: 1828 AN XY: 74468

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0179 Hom.: 19

Bravo AF: 0.0299

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs887541; hg19: chr3-52020604;