NM_000666.3:c.708-9A>G
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000666.3(ACY1):c.708-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,613,944 control chromosomes in the GnomAD database, including 4,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 2141 hom., cov: 33)
Exomes 𝑓: 0.031 ( 2597 hom. )
Consequence
ACY1
NM_000666.3 intron
NM_000666.3 intron
Scores
2
Splicing: ADA: 0.00001557
2
Clinical Significance
Conservation
PhyloP100: -1.88
Publications
8 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 3-51987300-A-G is Benign according to our data. Variant chr3-51987300-A-G is described in ClinVar as Benign. ClinVar VariationId is 256757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.107 AC: 16245AN: 152060Hom.: 2117 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
16245
AN:
152060
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0512 AC: 12863AN: 250992 AF XY: 0.0470 show subpopulations
GnomAD2 exomes
AF:
AC:
12863
AN:
250992
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0315 AC: 46042AN: 1461766Hom.: 2597 Cov.: 32 AF XY: 0.0315 AC XY: 22895AN XY: 727174 show subpopulations
GnomAD4 exome
AF:
AC:
46042
AN:
1461766
Hom.:
Cov.:
32
AF XY:
AC XY:
22895
AN XY:
727174
show subpopulations
African (AFR)
AF:
AC:
10702
AN:
33476
American (AMR)
AF:
AC:
1397
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
707
AN:
26136
East Asian (EAS)
AF:
AC:
2966
AN:
39700
South Asian (SAS)
AF:
AC:
5411
AN:
86256
European-Finnish (FIN)
AF:
AC:
993
AN:
53318
Middle Eastern (MID)
AF:
AC:
490
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
20346
AN:
1111998
Other (OTH)
AF:
AC:
3030
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
2760
5520
8279
11039
13799
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
954
1908
2862
3816
4770
<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 AF: 0.107 AC: 16317AN: 152178Hom.: 2141 Cov.: 33 AF XY: 0.105 AC XY: 7814AN XY: 74418 show subpopulations
GnomAD4 genome
AF:
AC:
16317
AN:
152178
Hom.:
Cov.:
33
AF XY:
AC XY:
7814
AN XY:
74418
show subpopulations
African (AFR)
AF:
AC:
12904
AN:
41464
American (AMR)
AF:
AC:
802
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
80
AN:
3470
East Asian (EAS)
AF:
AC:
373
AN:
5178
South Asian (SAS)
AF:
AC:
328
AN:
4828
European-Finnish (FIN)
AF:
AC:
176
AN:
10620
Middle Eastern (MID)
AF:
AC:
22
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1413
AN:
68002
Other (OTH)
AF:
AC:
198
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
615
1230
1844
2459
3074
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
162
324
486
648
810
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
384
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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