chr3-185192346-CCTGTA-AT

Position:

• chr3-185192346-CCTGTA-AT

Variant summary

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

The NM_001966.4(EHHADH):​c.2047_2052delTACAGGinsAT​(p.Tyr683fs) variant causes a frameshift, missense 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, missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.09

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]

ACMG classification

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	Protein	UniProt
EHHADH	NM_001966.4	c.2047_2052delTACAGGinsAT	p.Tyr683fs	frameshift_variant, missense_variant	7/7	ENST00000231887.8	NP_001957.2
EHHADH	NM_001166415.2	c.1759_1764delTACAGGinsAT	p.Tyr587fs	frameshift_variant, missense_variant	7/7		NP_001159887.1
EHHADH	XM_047447640.1	c.1423_1428delTACAGGinsAT	p.Tyr475fs	frameshift_variant, missense_variant	5/5		XP_047303596.1
EHHADH	XM_047447641.1	c.1423_1428delTACAGGinsAT	p.Tyr475fs	frameshift_variant, missense_variant	4/4		XP_047303597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHHADH	ENST00000231887.8	c.2047_2052delTACAGGinsAT	p.Tyr683fs	frameshift_variant, missense_variant	7/7	1	NM_001966.4	ENSP00000231887.3
EHHADH	ENST00000456310.5	c.1759_1764delTACAGGinsAT	p.Tyr587fs	frameshift_variant, missense_variant	7/7	2		ENSP00000387746.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

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

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-184910134;