chr16-89112123-C-T

Position:

chr16-89112123-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001243279.3(ACSF3):c.854C>T(p.Pro285Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0152 in 1,112,452 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 19 hom., cov: 0)

Exomes 𝑓: 0.014 ( 123 hom. )

Consequence

ACSF3
NM_001243279.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010101199).

BP6

Variant 16-89112123-C-T is Benign according to our data. Variant chr16-89112123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89112123-C-T is described in Lovd as [Benign]. Variant chr16-89112123-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.854C>T	p.Pro285Leu	missense_variant	5/11	ENST00000614302.5	NP_001230208.1	Q4G176

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5 link	c.854C>T	p.Pro285Leu	missense_variant	5/11	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.0873

AC:

1397

AN:

16008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.0987

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00716

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.0723

GnomAD3 exomes

AF:

0.00996

AC:

2326

AN:

233436

Hom.:

AF XY:

0.00972

AC XY:

1231

AN XY:

126676

show subpopulations

Gnomad AFR exome

AF:

0.00177

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.0141

AC:

15503

AN:

1096394

Hom.:

123

Cov.:

AF XY:

0.0143

AC XY:

7690

AN XY:

536310

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00300

Gnomad4 FIN exome

AF:

0.0897

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.0870

AC:

1397

AN:

16058

Hom.:

Cov.:

AF XY:

0.0955

AC XY:

767

AN XY:

8028

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.0485

Gnomad4 ASJ

AF:

0.0987

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00718

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.0690

Alfa

AF:

0.00981

Hom.:

Bravo

AF:

0.00653

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00875

AC:

1062

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 08, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -

Combined malonic and methylmalonic acidemia

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jun 02, 2020	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 07, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	ACSF3: BP4, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;T;T;.;T;T;.;T

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.089

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;.;D;D;.;D;D;D

MetaRNN

Benign

0.0010

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.4

.;L;L;.;L;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.3

D;D;.;D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0090

D;D;.;D;D;D;T;D

Sift4G

Uncertain

0.039

D;D;D;T;D;D;D;D

Polyphen

0.61

.;P;P;.;P;.;.;.

Vest4

0.69, 0.74

MPC

0.30

ClinPred

0.067

GERP RS

4.5

Varity_R

0.17

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Other links and lift over