chr20-34876769-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_018677.4(ACSS2):c.124C>A(p.Pro42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 1,413,066 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0040 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 4 hom. )
Consequence
ACSS2
NM_018677.4 missense
NM_018677.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: -0.0630
Genes affected
ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005499065).
BP6
?
Variant 20-34876769-C-A is Benign according to our data. Variant chr20-34876769-C-A is described in ClinVar as [Benign]. Clinvar id is 781546.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000405 (511/1260782) while in subpopulation AFR AF= 0.017 (425/25032). AF 95% confidence interval is 0.0156. There are 4 homozygotes in gnomad4_exome. There are 231 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACSS2 | NM_018677.4 | c.124C>A | p.Pro42Thr | missense_variant | 1/18 | ENST00000360596.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSS2 | ENST00000360596.7 | c.124C>A | p.Pro42Thr | missense_variant | 1/18 | 1 | NM_018677.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00400 AC: 609AN: 152166Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000410 AC: 23AN: 56076Hom.: 0 AF XY: 0.000340 AC XY: 11AN XY: 32380
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GnomAD4 exome AF: 0.000405 AC: 511AN: 1260782Hom.: 4 Cov.: 31 AF XY: 0.000376 AC XY: 231AN XY: 613894
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GnomAD4 genome ? AF: 0.00399 AC: 608AN: 152284Hom.: 2 Cov.: 32 AF XY: 0.00388 AC XY: 289AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;D;D;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;.;.;.
Vest4
MVP
MPC
1.8
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at