NM_001365788.1:c.1090C>T

Variant names:

• chr14-73619663-C-T
• rs576704472
• NM_001365788.1:c.1090C>T

Variant summary

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

The NM_001365788.1(ACOT6):​c.1090C>T​(p.Pro364Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ACOT6 NM_001365788.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• 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.1090C>T	p.Pro364Ser	missense	Exon 3 of 3	NP_001352717.1	Q3I5F7-1
	ACOT6	NM_001037162.1		c.448C>T	p.Pro150Ser	missense	Exon 2 of 2	NP_001032239.1	Q3I5F7-2
	ACOT6	NM_001365789.1		c.448C>T	p.Pro150Ser	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.1090C>T	p.Pro364Ser	missense	Exon 3 of 3	ENSP00000496277.1	Q3I5F7-1
	ACOT6	ENST00000381139.1	TSL:1	c.448C>T	p.Pro150Ser	missense	Exon 2 of 2	ENSP00000370531.1	Q3I5F7-2
	ACOT6	ENST00000554229.1	TSL:3	c.448C>T	p.Pro150Ser	missense	Exon 4 of 4	ENSP00000451464.1	G3V3W6

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000159 AC: 4 AN: 251408 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000289

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: 0.00000410 AC: 6 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727232

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74446

African (AFR) AF: 0.0000962 AC: 4 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

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	Uncertain	0.35
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.6
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MVP		0.19
MPC		0.90
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.80
gMVP		0.68
Mutation Taster		=82/18	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: rs576704472; hg19: chr14-74086367;