3-185192581-G-GC

Position:

• chr3-185192581-G-GC

Variant summary

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

The NM_001966.4(EHHADH):​c.1816_1817insG​(p.Thr606SerfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EHHADH NM_001966.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

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	UniProt
EHHADH	NM_001966.4	c.1816_1817insG	p.Thr606SerfsTer5	frameshift_variant	7/7	ENST00000231887.8
EHHADH	NM_001166415.2	c.1528_1529insG	p.Thr510SerfsTer5	frameshift_variant	7/7
EHHADH	XM_047447640.1	c.1192_1193insG	p.Thr398SerfsTer5	frameshift_variant	5/5
EHHADH	XM_047447641.1	c.1192_1193insG	p.Thr398SerfsTer5	frameshift_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHHADH	ENST00000231887.8	c.1816_1817insG	p.Thr606SerfsTer5	frameshift_variant	7/7	1	NM_001966.4	P1
EHHADH	ENST00000456310.5	c.1528_1529insG	p.Thr510SerfsTer5	frameshift_variant	7/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi renotubular syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553775828; hg19: chr3-184910369;