rs142287889

Variant names:

• chr16-89094080-T-A
• rs142287889
• NM_001243279.3:c.-194+84T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89094080-T-A
• chr16-89094080-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271
• 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF3	NM_001243279.3	MANE Select	c.-194+84T>A		intron	N/A	NP_001230208.1	Q4G176
	ACSF3	NM_001127214.4		c.-21+84T>A		intron	N/A	NP_001120686.1	Q4G176
	ACSF3	NM_174917.5		c.-194+88T>A		intron	N/A	NP_777577.2	Q4G176

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-194+84T>A		intron	N/A	ENSP00000479130.1	Q4G176
	ACSF3	ENST00000378345.8	TSL:1	c.-130+88T>A		intron	N/A	ENSP00000367596.4	F5H5A1
	ACSF3	ENST00000871966.1		c.-618T>A		5_prime_UTR	Exon 1 of 11	ENSP00000542025.1

Frequencies

GnomAD3 genomes AF: 0.00972 AC: 1459 AN: 150136 Hom.: 16 Cov.: 32

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: 9 AN: 630 Hom.: 0 AF XY: 0.0128 AC XY: 6 AN XY: 470

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 16

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.0164 AC: 9 AN: 548

Other (OTH) AF: 0.00 AC: 0 AN: 32

GnomAD4 genome AF: 0.00970 AC: 1457 AN: 150246 Hom.: 16 Cov.: 32 AF XY: 0.00908 AC XY: 666 AN XY: 73384

African (AFR) AF: 0.00177 AC: 73 AN: 41164

American (AMR) AF: 0.00695 AC: 105 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3462

East Asian (EAS) AF: 0.000394 AC: 2 AN: 5080

South Asian (SAS) AF: 0.0271 AC: 130 AN: 4804

European-Finnish (FIN) AF: 0.00231 AC: 23 AN: 9952

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.0150 AC: 1012 AN: 67386

Other (OTH) AF: 0.0101 AC: 21 AN: 2088

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00909

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.44
PhyloP100		-0.27
PromoterAI		-0.066	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142287889; hg19: chr16-89160488;