rs28938169

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006214.4(PHYH):c.85C>T(p.Pro29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,593,910 control chromosomes in the GnomAD database, including 23,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1806 hom., cov: 31)

Exomes 𝑓: 0.17 ( 21932 hom. )

Consequence

PHYH
NM_006214.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 2.37

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017195046).

BP6

Variant 10-13298236-G-A is Benign according to our data. Variant chr10-13298236-G-A is described in ClinVar as [Benign]. Clinvar id is 7582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-13298236-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYH	NM_006214.4 link	c.85C>T	p.Pro29Ser	missense_variant	Exon 2 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.85C>T	p.Pro29Ser	missense_variant	Exon 2 of 9	1	NM_006214.4	ENSP00000263038.4		O14832-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22292

AN:

152020

Hom.:

1803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.0923

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.148

AC:

37080

AN:

251292

Hom.:

3229

AF XY:

0.148

AC XY:

20038

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.0147

Gnomad SAS exome

AF:

0.0998

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.167

AC:

241357

AN:

1441772

Hom.:

21932

Cov.:

AF XY:

0.166

AC XY:

119198

AN XY:

718518

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.0147

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.147

AC:

22322

AN:

152138

Hom.:

1806

Cov.:

AF XY:

0.146

AC XY:

10856

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0193

Gnomad4 SAS

AF:

0.0932

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.165

Hom.:

3442

Bravo

AF:

0.137

TwinsUK

AF:

0.194

AC:

721

ALSPAC

AF:

0.172

AC:

664

ESP6500AA

AF:

0.122

AC:

539

ESP6500EA

AF:

0.177

AC:

1524

ExAC

AF:

0.149

AC:

18138

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

EpiCase

AF:

0.174

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Phytanic acid storage disease

Benign:5

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

This variant is interpreted as a Benign - Stand Alone, for Refsum disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. -

Mar 06, 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

- -

not provided

Benign:5

Sep 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10767344, 25525159, 20220177, 20981092, 11555634) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

May 01, 2000

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified

Benign:4

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. -

May 09, 2014

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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.25

T;T;.

Polyphen

0.047

B;B;.

Vest4

0.12

MPC

0.15

ClinPred

0.012

GERP RS

3.3

Varity_R

0.048

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over