Variant 16-89093730-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000537895.5(ACSF3):c.-130+5252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 150,808 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 7 hom., cov: 33)

Exomes 𝑓: 0.014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACSF3
ENST00000537895.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.977

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 16-89093730-G-A is Benign according to our data. Variant chr16-89093730-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1703310.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00549 (828/150808) while in subpopulation NFE AF= 0.00906 (608/67104). AF 95% confidence interval is 0.00846. There are 7 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000537895.5 link	c.-130+5252G>A		intron_variant	Intron 1 of 3	4		ENSP00000439201.1		F5H3B2

Frequencies

GnomAD3 genomes

AF:

0.00549

AC:

827

AN:

150704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.000484

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0136

AC:

AN:

660

Hom.:

AF XY:

0.0102

AC XY:

AN XY:

490

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:

0.0157

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00549

AC:

828

AN:

150808

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

424

AN XY:

73556

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.000293

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00962

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00449

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 24, 2022

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.9

DANN

Benign

0.90

Splicing

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