dbSNP rs10163373: ACSF3:c.-130+5329C>A (chr16-89093807-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000537895.5(ACSF3):c.-130+5329C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 170,270 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 249 hom., cov: 32)

Exomes 𝑓: 0.011 ( 12 hom. )

Consequence

ACSF3
ENST00000537895.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.997

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 16-89093807-C-A is Benign according to our data. Variant chr16-89093807-C-A is described in ClinVar as Benign. ClinVar VariationId is 1294308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000537895.5. 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.-383C>A	upstream_gene	N/A	NP_001230208.1	Q4G176
ACSF3	NM_001127214.4		c.-210C>A	upstream_gene	N/A	NP_001120686.1	Q4G176
ACSF3	NM_174917.5		c.-379C>A	upstream_gene	N/A	NP_777577.2	Q4G176

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSF3	ENST00000537895.5	TSL:4	c.-130+5329C>A	intron	N/A	ENSP00000439201.1	F5H3B2
ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-383C>A	upstream_gene	N/A	ENSP00000479130.1	Q4G176
ACSF3	ENST00000378345.8	TSL:1	c.-315C>A	upstream_gene	N/A	ENSP00000367596.4	F5H5A1

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4924

AN:

150624

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000592

Gnomad OTH

AF:

0.0241

GnomAD2 exomes

AF:

0.0150

AC:

AN:

2204

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.00385

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:

0.0167

GnomAD4 exome

AF:

0.0110

AC:

214

AN:

19538

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

161

AN XY:

14126

show subpopulations

African (AFR)

AF:

0.165

AC:

AN:

236

American (AMR)

AF:

0.00457

AC:

AN:

438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

276

East Asian (EAS)

AF:

0.00

AC:

AN:

524

South Asian (SAS)

AF:

0.0729

AC:

141

AN:

1934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

14916

Other (OTH)

AF:

0.0230

AC:

AN:

740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.615

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0329

AC:

4952

AN:

150732

Hom.:

249

Cov.:

AF XY:

0.0325

AC XY:

2394

AN XY:

73636

show subpopulations

African (AFR)

AF:

0.108

AC:

4450

AN:

41338

American (AMR)

AF:

0.0157

AC:

238

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.0354

AC:

171

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9946

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000592

AC:

AN:

67538

Other (OTH)

AF:

0.0239

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

226

451

677

902

1128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.00669

Hom.:

Bravo

AF:

0.0359

Asia WGS

AF:

0.0260

AC:

AN:

3400

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.0

PromoterAI

0.15

Neutral

(source)

Splicing

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