14-73537771-G-A

Position:

• chr14-73537771-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001037161.2(ACOT1):​c.350G>A​(p.Gly117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOT1 NM_001037161.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.219

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16861972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT1	NM_001037161.2	c.350G>A	p.Gly117Glu	missense_variant	1/3	ENST00000311148.9	NP_001032238.1
HEATR4	NM_001220484.1	c.-151-7527C>T		intron_variant		ENST00000553558.6	NP_001207413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT1	ENST00000311148.9	c.350G>A	p.Gly117Glu	missense_variant	1/3	1	NM_001037161.2	ENSP00000311224.4
HEATR4	ENST00000553558.6	c.-151-7527C>T		intron_variant		2	NM_001220484.1	ENSP00000450444.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1117442 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 555680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.350G>A (p.G117E) alteration is located in exon 1 (coding exon 1) of the ACOT1 gene. This alteration results from a G to A substitution at nucleotide position 350, causing the glycine (G) at amino acid position 117 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M;.
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.052
Sift	Benign	0.052	T;D
Sift4G	Benign	0.15	T;T
Polyphen		0.40	B;.
Vest4		0.050
MutPred		0.50		Gain of solvent accessibility (P = 0.005);Gain of solvent accessibility (P = 0.005);
MVP		0.53
ClinPred		1.0	D
GERP RS		0.66
Varity_R		0.20
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-74004475;