Variant chr16-89133188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001243279.3(ACSF3):c.1292C>T(p.Ser431Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACSF3
NM_001243279.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.83

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]

ACSF3 links:

ACSF3 (HGNC:):

ACSF3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSF3	NM_001243279.3 linkuse as main transcript	c.1292C>T	p.Ser431Phe	missense_variant	8/11	ENST00000614302.5	NP_001230208.1	Q4G176

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5 linkuse as main transcript	c.1292C>T	p.Ser431Phe	missense_variant	8/11	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251434

Hom.:

AF XY:

0.00

AC XY:

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:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727170

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.1292C>T (p.S431F) alteration is located in exon 8 (coding exon 6) of the ACSF3 gene. This alteration results from a C to T substitution at nucleotide position 1292, causing the serine (S) at amino acid position 431 to be replaced by a phenylalanine (F). 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

0.32

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;.;T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.77

LIST_S2

Pathogenic

0.98

.;D;D;.;D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.74

D;D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.0

M;M;.;M;.;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.2

D;.;D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0040

D;.;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D;D

Polyphen

0.96

D;D;.;D;.;.

Vest4

0.55

MutPred

0.68

Loss of phosphorylation at S431 (P = 0.012);Loss of phosphorylation at S431 (P = 0.012);.;Loss of phosphorylation at S431 (P = 0.012);.;.;

MVP

0.53

MPC

0.30

ClinPred

0.94

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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