14-73617186-T-C

Variant names:

• chr14-73617186-T-C
• NM_001365788.1:c.654T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001365788.1(ACOT6):​c.654T>C​(p.His218His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACOT6 NM_001365788.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.761
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 14-73617186-T-C is Benign according to our data. Variant chr14-73617186-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3772493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.761 with no splicing effect.

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.654T>C	p.His218His	synonymous	Exon 2 of 3	NP_001352717.1	Q3I5F7-1
	ACOT6	NM_001037162.1		c.12T>C	p.His4His	synonymous	Exon 1 of 2	NP_001032239.1	Q3I5F7-2
	ACOT6	NM_001365789.1		c.12T>C	p.His4His	synonymous	Exon 3 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.654T>C	p.His218His	synonymous	Exon 2 of 3	ENSP00000496277.1	Q3I5F7-1
	ACOT6	ENST00000381139.1	TSL:1	c.12T>C	p.His4His	synonymous	Exon 1 of 2	ENSP00000370531.1	Q3I5F7-2
	ACOT6	ENST00000554229.1	TSL:3	c.12T>C	p.His4His	synonymous	Exon 3 of 4	ENSP00000451464.1	G3V3W6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		-0.76
PromoterAI		-0.0048	Neutral

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

hg19: chr14-74083890;