dbSNP rs10163334: ACSF3:c.-130+5230C>T (chr16-89093708-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000537895.5(ACSF3):c.-130+5230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 151,764 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 0 hom. )

Consequence

ACSF3
ENST00000537895.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.246

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-89093708-C-T is Benign according to our data. Variant chr16-89093708-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1329720.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1740/151312) while in subpopulation AFR AF = 0.0351 (1457/41468). AF 95% confidence interval is 0.0336. There are 26 homozygotes in GnomAd4. There are 891 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR,AD gene

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.-482C>T	upstream_gene	N/A	NP_001230208.1	Q4G176
ACSF3	NM_001127214.4		c.-309C>T	upstream_gene	N/A	NP_001120686.1	Q4G176
ACSF3	NM_174917.5		c.-478C>T	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+5230C>T	intron	N/A	ENSP00000439201.1	F5H3B2
ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-482C>T	upstream_gene	N/A	ENSP00000479130.1	Q4G176
ACSF3	ENST00000378345.8	TSL:1	c.-414C>T	upstream_gene	N/A	ENSP00000367596.4	F5H5A1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1721

AN:

151210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00539

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000222

Gnomad OTH

AF:

0.00917

GnomAD4 exome

AF:

0.00664

AC:

AN:

452

Hom.:

AF XY:

0.00585

AC XY:

AN XY:

342

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00508

AC:

AN:

394

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0115

AC:

1740

AN:

151312

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

891

AN XY:

73898

show subpopulations

African (AFR)

AF:

0.0351

AC:

1457

AN:

41468

American (AMR)

AF:

0.00538

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.0346

AC:

167

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000222

AC:

AN:

67418

Other (OTH)

AF:

0.00907

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

175

262

350

437

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:

0.00840

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.0190

AC:

AN:

3456

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.1

(source)

DANN

Benign

0.88

PhyloP100

0.25

PromoterAI

-0.0078

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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