NM_001037161.2:c.52C>A

Variant names:

• chr14-73537473-C-A
• rs772023723
• NM_001037161.2:c.52C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001037161.2(ACOT1):​c.52C>A​(p.Pro18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000901 in 1,110,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000017 (1 hom., cov: 19)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOT1 NM_001037161.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

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.52C>A	p.Pro18Thr	missense	Exon 1 of 3	NP_001032238.1	E9KL42
	HEATR4	NM_001220484.1	MANE Select	c.-151-7229G>T		intron	N/A	NP_001207413.1	Q86WZ0
	HEATR4	NM_203309.2		c.-72-14249G>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.52C>A	p.Pro18Thr	missense	Exon 1 of 3	ENSP00000311224.4	Q86TX2
	ACOT1	ENST00000557556.1	TSL:1	c.52C>A	p.Pro18Thr	missense	Exon 1 of 3	ENSP00000451764.1	G3V4F2
	HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.-151-7229G>T		intron	N/A	ENSP00000450444.2	Q86WZ0

Frequencies

GnomAD3 genomes AF: 0.0000169 AC: 2 AN: 118068 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000185

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000780 AC: 1 AN: 128216 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000523

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.01e-7 AC: 1 AN: 1110474 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 550846

African (AFR) AF: 0.00 AC: 0 AN: 28748

American (AMR) AF: 0.0000365 AC: 1 AN: 27410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19648

East Asian (EAS) AF: 0.00 AC: 0 AN: 10502

South Asian (SAS) AF: 0.00 AC: 0 AN: 66758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 875486

Other (OTH) AF: 0.00 AC: 0 AN: 45266

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000169 AC: 2 AN: 118068 Hom.: 1 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 56898

African (AFR) AF: 0.00 AC: 0 AN: 36382

American (AMR) AF: 0.000185 AC: 2 AN: 10836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2738

East Asian (EAS) AF: 0.00 AC: 0 AN: 1458

South Asian (SAS) AF: 0.00 AC: 0 AN: 3860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53332

Other (OTH) AF: 0.00 AC: 0 AN: 1594

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000229 AC: 2

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	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		3.5
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.62		Gain of catalytic residue at W15 (P = 0)
MVP		0.83
ClinPred		0.98	D
GERP RS		2.7
PromoterAI		0.042	Neutral
Varity_R		0.61
gMVP		0.54
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs772023723; hg19: chr14-74004177;