U.S. flag

An official website of the United States government

NM_006214.4(PHYH):c.574G>A (p.Ala192Thr) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 27, 2022
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:
RCV000483319.5

Allele description [Variation Report for NM_006214.4(PHYH):c.574G>A (p.Ala192Thr)]

NM_006214.4(PHYH):c.574G>A (p.Ala192Thr)

Gene:
PHYH:phytanoyl-CoA 2-hydroxylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_006214.4(PHYH):c.574G>A (p.Ala192Thr)
HGVS:
  • NC_000010.11:g.13288464C>T
  • NG_012862.1:g.16667G>A
  • NM_001037537.2:c.274G>A
  • NM_001323080.2:c.274G>A
  • NM_001323082.2:c.580G>A
  • NM_001323083.2:c.415-4625G>A
  • NM_001323084.2:c.280G>A
  • NM_006214.4:c.574G>AMANE SELECT
  • NP_001032626.1:p.Ala92Thr
  • NP_001310009.1:p.Ala92Thr
  • NP_001310011.1:p.Ala194Thr
  • NP_001310013.1:p.Ala94Thr
  • NP_006205.1:p.Ala192Thr
  • NC_000010.10:g.13330464C>T
  • NM_006214.3:c.574G>A
Protein change:
A192T
Links:
dbSNP: rs751660253
NCBI 1000 Genomes Browser:
rs751660253
Molecular consequence:
  • NM_001323083.2:c.415-4625G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001037537.2:c.274G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323080.2:c.274G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323082.2:c.580G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323084.2:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006214.4:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000573091GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(Feb 16, 2017) 		germlineclinical testing

Citation Link,

SCV001398501Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 27, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 GeneDx, SCV000573091.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The A192T variant in the PHYH gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A192T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A192T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A192T as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001398501.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 192 of the PHYH protein (p.Ala192Thr). This variant is present in population databases (rs751660253, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PHYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 299253). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PHYH protein function. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024