NM_001037161.2:c.679G>A

Variant names:

• chr14-73543068-G-A
• NM_001037161.2:c.679G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001037161.2(ACOT1):​c.679G>A​(p.Gly227Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 19)
• Consequence: ACOT1 NM_001037161.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.35
• Publications: 0 publications found

Genes affected

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299171 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037161.2. 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
	ACOT1	NM_001037161.2	MANE Select	c.679G>A	p.Gly227Arg	missense	Exon 3 of 3	NP_001032238.1	E9KL42
	HEATR4	NM_001220484.1	MANE Select	c.-151-12824C>T		intron	N/A	NP_001207413.1	Q86WZ0
	HEATR4	NM_203309.2		c.-73+15683C>T		intron	N/A	NP_976054.2	Q86WZ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT1	ENST00000311148.9	TSL:1 MANE Select	c.679G>A	p.Gly227Arg	missense	Exon 3 of 3	ENSP00000311224.4	Q86TX2
	HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.-151-12824C>T		intron	N/A	ENSP00000450444.2	Q86WZ0
	HEATR4	ENST00000334988.2	TSL:1	c.-73+15683C>T		intron	N/A	ENSP00000335447.2	Q86WZ0

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
PhyloP100		5.3
Varity_R		0.92
gMVP		0.97
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-74009772;