Variant 16-89094080-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001243279.3(ACSF3):c.-194+84T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00972 in 150,876 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 16 hom., cov: 32)

Exomes 𝑓: 0.014 ( 0 hom. )

Consequence

ACSF3
NM_001243279.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.271

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-89094080-T-A is Benign according to our data. Variant chr16-89094080-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1687680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0097 (1457/150246) while in subpopulation SAS AF= 0.0271 (130/4804). AF 95% confidence interval is 0.0233. There are 16 homozygotes in gnomad4. There are 666 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.-194+84T>A		intron_variant	Intron 1 of 10	ENST00000614302.5	NP_001230208.1	Q4G176

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5 link	c.-194+84T>A		intron_variant	Intron 1 of 10	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.00972

AC:

1459

AN:

150136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.00696

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.00231

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0102

GnomAD4 exome

AF:

0.0143

AC:

AN:

630

Hom.:

AF XY:

0.0128

AC XY:

AN XY:

470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00970

AC:

1457

AN:

150246

Hom.:

Cov.:

AF XY:

0.00908

AC XY:

666

AN XY:

73384

show subpopulations

Gnomad4 AFR

AF:

0.00177

Gnomad4 AMR

AF:

0.00695

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000394

Gnomad4 SAS

AF:

0.0271

Gnomad4 FIN

AF:

0.00231

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0101

Alfa

AF:

0.00470

Hom.:

Bravo

AF:

0.00909

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 24, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.2

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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