Genetic Variant ACSF3:c.-269C>T (chr16-89093921-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001243279.3(ACSF3):c.-269C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACSF3
NM_001243279.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.368

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.-269C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001230208.1	Q4G176
ACSF3	NM_001243279.3	MANE Select	c.-269C>T	5_prime_UTR	Exon 1 of 11	NP_001230208.1	Q4G176
ACSF3	NM_001127214.4		c.-96C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001120686.1	Q4G176

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-269C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000479130.1	Q4G176
ACSF3	ENST00000378345.8	TSL:1	c.-201C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000367596.4	F5H5A1
ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-269C>T	5_prime_UTR	Exon 1 of 11	ENSP00000479130.1	Q4G176

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

175848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

107630

African (AFR)

AF:

0.00

AC:

AN:

3640

American (AMR)

AF:

0.00

AC:

AN:

16018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7564

East Asian (EAS)

AF:

0.00

AC:

AN:

1236

South Asian (SAS)

AF:

0.00

AC:

AN:

42026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

710

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

89012

Other (OTH)

AF:

0.00

AC:

AN:

7278

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.37

PromoterAI

0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over