ENST00000537895.5:c.-130+5329C>T

Variant names:

• chr16-89093807-C-T
• rs10163373
• ENST00000537895.5:c.-130+5329C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000537895.5(ACSF3):​c.-130+5329C>T variant causes a intron 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 ENST00000537895.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 0 publications found

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)

ACMG classification

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=-0.63).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF3	NM_001243279.3	MANE Select	c.-383C>T		upstream_gene	N/A	NP_001230208.1	Q4G176
	ACSF3	NM_001127214.4		c.-210C>T		upstream_gene	N/A	NP_001120686.1	Q4G176
	ACSF3	NM_174917.5		c.-379C>T		upstream_gene	N/A	NP_777577.2	Q4G176

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 19538 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14126

African (AFR) AF: 0.00 AC: 0 AN: 236

American (AMR) AF: 0.00 AC: 0 AN: 438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 276

East Asian (EAS) AF: 0.00 AC: 0 AN: 524

South Asian (SAS) AF: 0.00 AC: 0 AN: 1934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14916

Other (OTH) AF: 0.00 AC: 0 AN: 740

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		1.0
PromoterAI		-0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10163373; hg19: chr16-89160215;