10-13288402-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006214.4(PHYH):c.636A>G(p.Thr212Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,613,770 control chromosomes in the GnomAD database, including 53,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6431 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47302 hom. )

Consequence

PHYH
NM_006214.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -3.16

Publications

22 publications found

Variant links:

Genes affected

PHYH (HGNC:8940): (phytanoyl-CoA 2-hydroxylase) This gene is a member of the PhyH family and encodes a peroxisomal protein that is involved in the alpha-oxidation of 3-methyl branched fatty acids. Specifically, this protein converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. Mutations in this gene have been associated with Refsum disease (RD) and deficient protein activity has been associated with Zellweger syndrome and rhizomelic chondrodysplasia punctata. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

PHYH Gene-Disease associations (from GenCC):

adult Refsum disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet
phytanoyl-CoA hydroxylase deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

PHYH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 10-13288402-T-C is Benign according to our data. Variant chr10-13288402-T-C is described in ClinVar as Benign. ClinVar VariationId is 95349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYH	NM_006214.4 link	c.636A>G	p.Thr212Thr	synonymous_variant	Exon 6 of 9	ENST00000263038.9	NP_006205.1	O14832-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYH	ENST00000263038.9 link	c.636A>G	p.Thr212Thr	synonymous_variant	Exon 6 of 9	1	NM_006214.4	ENSP00000263038.4		O14832-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42556

AN:

152004

Hom.:

6413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.233

AC:

58616

AN:

251216

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.401

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.0891

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.249

AC:

364641

AN:

1461648

Hom.:

47302

Cov.:

AF XY:

0.246

AC XY:

179092

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.401

AC:

13425

AN:

33472

American (AMR)

AF:

0.189

AC:

8435

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

5904

AN:

26134

East Asian (EAS)

AF:

0.146

AC:

5804

AN:

39698

South Asian (SAS)

AF:

0.159

AC:

13702

AN:

86244

European-Finnish (FIN)

AF:

0.280

AC:

14929

AN:

53406

Middle Eastern (MID)

AF:

0.198

AC:

1123

AN:

5686

European-Non Finnish (NFE)

AF:

0.258

AC:

286847

AN:

1111896

Other (OTH)

AF:

0.240

AC:

14472

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14939

29878

44816

59755

74694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9568

19136

28704

38272

47840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42622

AN:

152122

Hom.:

6431

Cov.:

AF XY:

0.277

AC XY:

20631

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.393

AC:

16303

AN:

41470

American (AMR)

AF:

0.192

AC:

2936

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

796

AN:

3472

East Asian (EAS)

AF:

0.121

AC:

624

AN:

5162

South Asian (SAS)

AF:

0.159

AC:

767

AN:

4824

European-Finnish (FIN)

AF:

0.276

AC:

2922

AN:

10592

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17537

AN:

67994

Other (OTH)

AF:

0.235

AC:

497

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1538

3076

4614

6152

7690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.255

Hom.:

14922

Bravo

AF:

0.278

Asia WGS

AF:

0.165

AC:

571

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.236

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 19, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Phytanic acid storage disease

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.3

(source)

DANN

Benign

0.40

PhyloP100

-3.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over