Variant 3-185192346-CCTGTA-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001966.4(EHHADH):c.2047_2052delinsAT(p.Tyr683IlefsTer15) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

EHHADH
NM_001966.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

EHHADH (HGNC:3247): (enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase) The protein encoded by this gene is a bifunctional enzyme and is one of the four enzymes of the peroxisomal beta-oxidation pathway. The N-terminal region of the encoded protein contains enoyl-CoA hydratase activity while the C-terminal region contains 3-hydroxyacyl-CoA dehydrogenase activity. Defects in this gene are a cause of peroxisomal disorders such as Zellweger syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

EHHADH links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EHHADH	NM_001966.4 linkuse as main transcript	c.2047_2052delinsAT	p.Tyr683IlefsTer15	frameshift_variant	7/7	ENST00000231887.8
EHHADH	NM_001166415.2 linkuse as main transcript	c.1759_1764delinsAT	p.Tyr587IlefsTer15	frameshift_variant	7/7
EHHADH	XM_047447640.1 linkuse as main transcript	c.1423_1428delinsAT	p.Tyr475IlefsTer15	frameshift_variant	5/5
EHHADH	XM_047447641.1 linkuse as main transcript	c.1423_1428delinsAT	p.Tyr475IlefsTer15	frameshift_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8 linkuse as main transcript	c.2047_2052delinsAT	p.Tyr683IlefsTer15	frameshift_variant	7/7	1	NM_001966.4	P1	Q08426-1
EHHADH	ENST00000456310.5 linkuse as main transcript	c.1759_1764delinsAT	p.Tyr587IlefsTer15	frameshift_variant	7/7	2			Q08426-2

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EHHADH-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 29, 2024

The EHHADH c.2047_2052delinsAT variant is predicted to result in a frameshift and premature protein termination (p.Tyr683Ilefs*15). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

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

No publications associated with this variant yet.