17-41892379-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001096.3(ACLY):c.1670C>T(p.Ala557Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,674 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ACLY
NM_001096.3 missense
NM_001096.3 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 4.36
Genes affected
ACLY (HGNC:115): (ATP citrate lyase) ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Dec 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ACLY
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30374163).
BS2
?
High AC in GnomAd at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACLY | NM_001096.3 | c.1670C>T | p.Ala557Val | missense_variant | 16/29 | ENST00000352035.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACLY | ENST00000352035.7 | c.1670C>T | p.Ala557Val | missense_variant | 16/29 | 1 | NM_001096.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000790 AC: 12AN: 151944Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
12
AN:
151944
Hom.:
Cov.:
31
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:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461730Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 exome
AF:
AC:
3
AN:
1461730
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727186
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000790 AC: 12AN: 151944Hom.: 0 Cov.: 31 AF XY: 0.0000809 AC XY: 6AN XY: 74180
GnomAD4 genome
?
AF:
AC:
12
AN:
151944
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
74180
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2022 | The c.1670C>T (p.A557V) alteration is located in exon 16 (coding exon 15) of the ACLY gene. This alteration results from a C to T substitution at nucleotide position 1670, causing the alanine (A) at amino acid position 557 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;D;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D
REVEL
Uncertain
Sift
Benign
T;.;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;.;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at