rs143793502

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. P285P) has been classified 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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

combined malonic and methylmalonic acidemia
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACSF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 381877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243279.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSF3	NM_001243279.3	MANE Select	c.854C>T	p.Pro285Leu	missense	Exon 5 of 11	NP_001230208.1	Q4G176
ACSF3	NM_001127214.4		c.854C>T	p.Pro285Leu	missense	Exon 4 of 10	NP_001120686.1	Q4G176
ACSF3	NM_174917.5		c.854C>T	p.Pro285Leu	missense	Exon 5 of 11	NP_777577.2	Q4G176

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.854C>T	p.Pro285Leu	missense	Exon 5 of 11	ENSP00000479130.1	Q4G176
ACSF3	ENST00000378345.8	TSL:1	c.59C>T	p.Pro20Leu	missense	Exon 3 of 9	ENSP00000367596.4	F5H5A1
ACSF3	ENST00000871968.1		c.854C>T	p.Pro285Leu	missense	Exon 5 of 12	ENSP00000542027.1

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

GnomAD2 exomes

AF:

0.00996

AC:

2326

AN:

233436

AF XY:

0.00972

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 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

African (AFR)

AF:

0.00182

AC:

AN:

24212

American (AMR)

AF:

0.00273

AC:

AN:

28570

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

184

AN:

15226

East Asian (EAS)

AF:

0.00

AC:

AN:

17202

South Asian (SAS)

AF:

0.00300

AC:

158

AN:

52686

European-Finnish (FIN)

AF:

0.0897

AC:

2189

AN:

24396

Middle Eastern (MID)

AF:

0.00127

AC:

AN:

3924

European-Non Finnish (NFE)

AF:

0.0139

AC:

12351

AN:

890676

Other (OTH)

AF:

0.0125

AC:

494

AN:

39502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

926

1852

2779

3705

4631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0870

AC:

1397

AN:

16058

Hom.:

Cov.:

AF XY:

0.0955

AC XY:

767

AN XY:

8028

show subpopulations

African (AFR)

AF:

0.0121

AC:

AN:

6202

American (AMR)

AF:

0.0485

AC:

AN:

990

Ashkenazi Jewish (ASJ)

AF:

0.0987

AC:

AN:

314

East Asian (EAS)

AF:

0.00

AC:

AN:

798

South Asian (SAS)

AF:

0.00718

AC:

AN:

836

European-Finnish (FIN)

AF:

0.385

AC:

430

AN:

1118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.143

AC:

795

AN:

5556

Other (OTH)

AF:

0.0690

AC:

AN:

174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

138

207

276

345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00910

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined malonic and methylmalonic acidemia (3)

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.089

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0010

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.4

PhyloP100

5.2

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.3

REVEL

Benign

0.27

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.039

Polyphen

0.61

Vest4

0.69

MPC

0.30

ClinPred

0.067

GERP RS

4.5

Varity_R

0.17

gMVP

0.72

Mutation Taster

=66/34

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over