NM_006214.4(PHYH):c.734G>A (p.Arg245Gln) AND Phytanic acid storage disease

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Sep 1, 2024
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:: RCV000665931.13

Allele description [Variation Report for NM_006214.4(PHYH):c.734G>A (p.Arg245Gln)]

NM_006214.4(PHYH):c.734G>A (p.Arg245Gln)

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.734G>A (p.Arg245Gln)

HGVS:

NC_000010.11:g.13283784C>T
NG_012862.1:g.21347G>A
NM_001037537.2:c.434G>A
NM_001323080.2:c.434G>A
NM_001323082.2:c.740G>A
NM_001323083.2:c.470G>A
NM_001323084.2:c.440G>A
NM_006214.4:c.734G>AMANE SELECT
NP_001032626.1:p.Arg145Gln
NP_001032626.1:p.Arg145Gln
NP_001310009.1:p.Arg145Gln
NP_001310011.1:p.Arg247Gln
NP_001310012.1:p.Arg157Gln
NP_001310013.1:p.Arg147Gln
NP_006205.1:p.Arg245Gln
NC_000010.10:g.13325784C>T
NM_001037537.1:c.434G>A
NM_006214.3:c.734G>A
O14832:p.Arg245Gln

Protein change:

R145Q

Links:

UniProtKB: O14832#VAR_017491; dbSNP: rs62619919

NCBI 1000 Genomes Browser:

rs62619919

Molecular consequence:

NM_001037537.2:c.434G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323080.2:c.434G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323082.2:c.740G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323083.2:c.470G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323084.2:c.440G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006214.4:c.734G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Phytanic acid storage disease
Synonyms:: HMSN IV; REFSUM DISEASE, CLASSIC; Disorder of cornification 11 (phytanic acid type); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009958; MedGen: C0034960; Orphanet: 773; OMIM: 266500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000790142	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely benign (Mar 6, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10767344, 14974078, 16186124 Citation Link,
SCV000845255	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Sep 1, 2024)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004812635	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (May 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000790142

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely benign
(Mar 6, 2017)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000845255

Genomic Research Center, Shahid Beheshti University of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Sep 1, 2024)

inherited

clinical testing

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

SCV004812635

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(May 4, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	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

Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7).

Jansen GA, Waterham HR, Wanders RJ.

Hum Mutat. 2004 Mar;23(3):209-18. Review.

PubMed [citation]

PMID:: 14974078

Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease.

McDonough MA, Kavanagh KL, Butler D, Searls T, Oppermann U, Schofield CJ.

J Biol Chem. 2005 Dec 9;280(49):41101-10. Epub 2005 Sep 25.

PubMed [citation]

PMID:: 16186124

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000790142.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000845255.2

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

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

From Illumina Laboratory Services, Illumina, SCV001264065.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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 Molecular Genetics, Royal Melbourne Hospital, SCV004812635.1

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

Description

South Asian population allele frequency is 1.166% (rs62619919, 389/30616 alleles, 6 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1

#	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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001264065	Illumina Laboratory Services, Illumina	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001264065

Illumina Laboratory Services, Illumina

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link

Last Updated: Nov 3, 2024

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