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GeneBe

20-25007871-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032501.4(ACSS1):​c.1961G>T​(p.Ser654Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACSS1
NM_032501.4 missense

Scores

1
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.348
Variant links:
Genes affected
ACSS1 (HGNC:16091): (acyl-CoA synthetase short chain family member 1) This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14961234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACSS1NM_032501.4 linkuse as main transcriptc.1961G>T p.Ser654Ile missense_variant 14/14 ENST00000323482.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACSS1ENST00000323482.9 linkuse as main transcriptc.1961G>T p.Ser654Ile missense_variant 14/141 NM_032501.4 P1Q9NUB1-1
ACSS1ENST00000484396.1 linkuse as main transcriptn.3128G>T non_coding_transcript_exon_variant 2/21
ACSS1ENST00000537502.5 linkuse as main transcriptc.1598G>T p.Ser533Ile missense_variant 13/132 Q9NUB1-3
ACSS1ENST00000432802.6 linkuse as main transcriptc.1663-946G>T intron_variant 2 Q9NUB1-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251470
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
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:
0.00000205
AC:
3
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsNov 27, 2023The c.1961G>T (p.S654I) alteration is located in exon 14 (coding exon 14) of the ACSS1 gene. This alteration results from a G to T substitution at nucleotide position 1961, causing the serine (S) at amino acid position 654 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Uncertain
0.98
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.13
N
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.28
T
REVEL
Benign
0.077
Sift4G
Uncertain
0.018
D;D
Polyphen
0.66
.;P
Vest4
0.11
MutPred
0.44
.;Loss of disorder (P = 0.0272);
MVP
0.69
MPC
0.90
ClinPred
0.29
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.20

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775295429; hg19: chr20-24988507; API