Variant chr14-73537825-GGCGCGAGCCGGTGC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The ENST00000311148.9(ACOT1):c.410_423del(p.Glu137GlyfsTer35) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACOT1
ENST00000311148.9 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.33

Variant links:

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]

ACOT1 links:

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 14-73537825-GGCGCGAGCCGGTGC-G is Pathogenic according to our data. Variant chr14-73537825-GGCGCGAGCCGGTGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 375394.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-73537825-GGCGCGAGCCGGTGC-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT1	NM_001037161.2 linkuse as main transcript	c.410_423del	p.Glu137GlyfsTer35	frameshift_variant	1/3	ENST00000311148.9	NP_001032238.1
HEATR4	NM_001220484.1 linkuse as main transcript	c.-151-7595_-151-7582del		intron_variant		ENST00000553558.6	NP_001207413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT1	ENST00000311148.9 linkuse as main transcript	c.410_423del	p.Glu137GlyfsTer35	frameshift_variant	1/3	1	NM_001037161.2	ENSP00000311224	P1
HEATR4	ENST00000553558.6 linkuse as main transcript	c.-151-7595_-151-7582del		intron_variant		2	NM_001220484.1	ENSP00000450444	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.17e-7

AC:

AN:

1089988

Hom.:

AF XY:

0.00

AC XY:

AN XY:

540198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000368

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.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Generalized hypotonia

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

This variant was identified as homozygous in an individual with congenital hypotonia and concern for mitochondrial myopathy. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over