chr16-89114475-G-T

Variant summary

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

The NM_001243279.3(ACSF3):​c.1114G>T​(p.Val372Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V372M) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ACSF3
NM_001243279.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.533
Variant links:
Genes affected
ACSF3 (HGNC:27288): (acyl-CoA synthetase family member 3) This gene encodes a member of the acyl-CoA synthetase family of enzymes that activate fatty acids by catalyzing the formation of a thioester linkage between fatty acids and coenzyme A. The encoded protein is localized to mitochondria, has high specificity for malonate and methylmalonate and possesses malonyl-CoA synthetase activity. Mutations in this gene are a cause of combined malonic and methylmalonic aciduria. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Sep 2013]

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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=0.12272009).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACSF3NM_001243279.3 linkc.1114G>T p.Val372Leu missense_variant Exon 6 of 11 ENST00000614302.5 NP_001230208.1 Q4G176

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACSF3ENST00000614302.5 linkc.1114G>T p.Val372Leu missense_variant Exon 6 of 11 5 NM_001243279.3 ENSP00000479130.1 Q4G176

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.85e-7
AC:
1
AN:
1460192
Hom.:
0
Cov.:
79
AF XY:
0.00000138
AC XY:
1
AN XY:
726542
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
1.2
DANN
Benign
0.79
DEOGEN2
Benign
0.049
T;T;.;T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.34
.;T;T;.;T;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.12
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.11
N;N;.;N;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.80
N;.;N;N;N;N
REVEL
Benign
0.028
Sift
Benign
0.27
T;.;T;T;T;T
Sift4G
Benign
0.23
T;T;T;T;T;T
Polyphen
0.0010
B;B;.;B;.;.
Vest4
0.15
MutPred
0.35
Loss of glycosylation at T370 (P = 0.1458);Loss of glycosylation at T370 (P = 0.1458);.;Loss of glycosylation at T370 (P = 0.1458);.;.;
MVP
0.18
MPC
0.065
ClinPred
0.048
T
GERP RS
-0.27
Varity_R
0.085
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs3743979; hg19: chr16-89180883; API