Genetic Variant ACSF3:c.-194+14G>C (chr16-89094010-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001243279.3(ACSF3):c.-194+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 169,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

ACSF3
NM_001243279.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.26

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-89094010-G-C is Benign according to our data. Variant chr16-89094010-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 516974.Status of the report is criteria_provided_single_submitter, 1 stars.

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	Effect	Exon Rank	Protein	UniProt
ACSF3	NM_001243279.3	MANE Select	c.-194+14G>C	intron	N/A	NP_001230208.1	Q4G176
ACSF3	NM_001127214.4		c.-21+14G>C	intron	N/A	NP_001120686.1	Q4G176
ACSF3	NM_174917.5		c.-194+18G>C	intron	N/A	NP_777577.2	Q4G176

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-194+14G>C	intron	N/A	ENSP00000479130.1	Q4G176
ACSF3	ENST00000378345.8	TSL:1	c.-130+18G>C	intron	N/A	ENSP00000367596.4	F5H5A1
ACSF3	ENST00000871966.1		c.-688G>C	5_prime_UTR	Exon 1 of 11	ENSP00000542025.1

Frequencies

GnomAD3 genomes

AF:

0.000215

AC:

AN:

148666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000255

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000465

AC:

AN:

6446

AF XY:

0.000701

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00500

GnomAD4 exome

AF:

0.000520

AC:

AN:

21148

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

AN XY:

14650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

368

American (AMR)

AF:

0.00

AC:

AN:

948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

680

East Asian (EAS)

AF:

0.00

AC:

AN:

340

South Asian (SAS)

AF:

0.00180

AC:

AN:

3886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

106

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

13256

Other (OTH)

AF:

0.00130

AC:

AN:

770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000208

AC:

AN:

148772

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

AN XY:

72534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41032

American (AMR)

AF:

0.000133

AC:

AN:

15002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00228

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9440

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000255

AC:

AN:

66666

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000285

Hom.:

Bravo

AF:

0.000151

Asia WGS

AF:

0.000661

AC:

AN:

3040

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.78

(source)

DANN

Benign

0.35

PhyloP100

-3.3

PromoterAI

-0.24

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over