rs28938169

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The ENST00000263038.9(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 (★★). Synonymous variant affecting the same amino acid position (i.e. P29P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.15 ( 1806 hom., cov: 31)

Exomes 𝑓: 0.17 ( 21932 hom. )

Consequence

PHYH
ENST00000263038.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.37

Publications

21 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 (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 VariationId is 7582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263038.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PHYH	NM_006214.4	MANE Select	c.85C>T	p.Pro29Ser	missense	Exon 2 of 9	NP_006205.1
PHYH	NM_001323082.2		c.85C>T	p.Pro29Ser	missense	Exon 2 of 9	NP_001310011.1
PHYH	NM_001323083.2		c.85C>T	p.Pro29Ser	missense	Exon 2 of 7	NP_001310012.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PHYH	ENST00000263038.9	TSL:1 MANE Select	c.85C>T	p.Pro29Ser	missense	Exon 2 of 9	ENSP00000263038.4
PHYH	ENST00000396920.7	TSL:5	c.28C>T	p.Pro10Ser	missense	Exon 2 of 9	ENSP00000380126.3
PHYH	ENST00000479604.1	TSL:3	c.85C>T	p.Pro29Ser	missense	Exon 2 of 6	ENSP00000420117.1

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

GnomAD2 exomes

AF:

0.148

AC:

37080

AN:

251292

AF XY:

0.148

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 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

African (AFR)

AF:

0.115

AC:

3816

AN:

33124

American (AMR)

AF:

0.112

AC:

4982

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3860

AN:

25978

East Asian (EAS)

AF:

0.0147

AC:

584

AN:

39634

South Asian (SAS)

AF:

0.102

AC:

8735

AN:

85962

European-Finnish (FIN)

AF:

0.230

AC:

12244

AN:

53248

Middle Eastern (MID)

AF:

0.103

AC:

591

AN:

5730

European-Non Finnish (NFE)

AF:

0.181

AC:

197413

AN:

1093676

Other (OTH)

AF:

0.153

AC:

9132

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

8721

17441

26162

34882

43603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6788

13576

20364

27152

33940

<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:

0.147

AC:

22322

AN:

152138

Hom.:

1806

Cov.:

AF XY:

0.146

AC XY:

10856

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.118

AC:

4904

AN:

41510

American (AMR)

AF:

0.100

AC:

1529

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

500

AN:

3472

East Asian (EAS)

AF:

0.0193

AC:

100

AN:

5178

South Asian (SAS)

AF:

0.0932

AC:

449

AN:

4816

European-Finnish (FIN)

AF:

0.220

AC:

2325

AN:

10566

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12128

AN:

68002

Other (OTH)

AF:

0.133

AC:

280

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

979

1958

2936

3915

4894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.165

Hom.:

7122

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Phytanic acid storage disease (5)

not specified (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.38

Sift

Benign

0.28

Sift4G

Benign

0.25

Polyphen

0.047

Vest4

0.12

MPC

0.15

ClinPred

0.012

GERP RS

3.3

Varity_R

0.048

gMVP

0.50

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over