NM_004092.4(ECHS1):c.82G>T (p.Ala28Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 4, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002004789.5

Allele description [Variation Report for NM_004092.4(ECHS1):c.82G>T (p.Ala28Ser)]

NM_004092.4(ECHS1):c.82G>T (p.Ala28Ser)

Genes:

LOC130005023:ATAC-STARR-seq lymphoblastoid silent region 2977 [Gene]
ECHS1:enoyl-CoA hydratase, short chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.3

Genomic location:

Preferred name:

NM_004092.4(ECHS1):c.82G>T (p.Ala28Ser)

HGVS:

NC_000010.11:g.133373252C>A
NG_042077.1:g.5153G>T
NM_004092.3:c.82G>T
NM_004092.4:c.82G>TMANE SELECT
NP_004083.3:p.Ala28Ser
NC_000010.10:g.135186756C>A

Protein change:

A28S

Links:

dbSNP: rs772023125

NCBI 1000 Genomes Browser:

rs772023125

Molecular consequence:

NM_004092.4:c.82G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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G-protein coupled receptor 176 isoform X1 [Homo sapiens]
G-protein coupled receptor 176 isoform X1 [Homo sapiens]
gi|1034589568|ref|XP_016877362.1|

Protein
JGI_CAAN665.rev NIH_XGC_tropTe4 Xenopus tropicalis cDNA clone IMAGE:7686434 3', ...
JGI_CAAN665.rev NIH_XGC_tropTe4 Xenopus tropicalis cDNA clone IMAGE:7686434 3', mRNA sequence
gi|58647318|gnl|dbEST|27614893|gb|C 74.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236842	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 20, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004035615	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 4, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236842

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 20, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004035615

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 4, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236842.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces alanine with serine at codon 28 of the ECHS1 protein (p.Ala28Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. While this variant is present in population databases (rs772023125), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with ECHS1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV004035615.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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