14-73619405-G-T

Variant names:

• chr14-73619405-G-T
• rs1890593127
• NM_001365788.1:c.832G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001365788.1(ACOT6):​c.832G>T​(p.Asp278Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D278H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACOT6 NM_001365788.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918
• Publications: 0 publications found

Genes affected

ACOT6 (HGNC:33159): (acyl-CoA thioesterase 6) Predicted to enable acyl-CoA hydrolase activity. Predicted to be involved in acyl-CoA metabolic process and 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]

ENSG00000258603 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365788.1. 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
	ACOT6	NM_001365788.1	MANE Select	c.832G>T	p.Asp278Tyr	missense	Exon 3 of 3	NP_001352717.1	Q3I5F7-1
	ACOT6	NM_001037162.1		c.190G>T	p.Asp64Tyr	missense	Exon 2 of 2	NP_001032239.1	Q3I5F7-2
	ACOT6	NM_001365789.1		c.190G>T	p.Asp64Tyr	missense	Exon 4 of 4	NP_001352718.1	Q3I5F7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT6	ENST00000645972.2	MANE Select	c.832G>T	p.Asp278Tyr	missense	Exon 3 of 3	ENSP00000496277.1	Q3I5F7-1
	ACOT6	ENST00000381139.1	TSL:1	c.190G>T	p.Asp64Tyr	missense	Exon 2 of 2	ENSP00000370531.1	Q3I5F7-2
	ACOT6	ENST00000554229.1	TSL:3	c.190G>T	p.Asp64Tyr	missense	Exon 4 of 4	ENSP00000451464.1	G3V3W6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.92
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.26
Sift	Benign	0.080	T
Sift4G	Benign	0.087	T
Polyphen		0.98	D
Vest4		0.56
MutPred		0.54		Gain of methylation at K69 (P = 0.0672)
MVP		0.18
MPC		0.96
ClinPred		0.79	D
GERP RS		3.9
Varity_R		0.39
gMVP		0.69
Mutation Taster		=79/21	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: rs1890593127; hg19: chr14-74086109;