Genetic Variant PHYH:c.678+69C>A (chr10-13288291-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_006214.4(PHYH):c.678+69C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,317,672 control chromosomes in the GnomAD database, including 41,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5838 hom., cov: 33)

Exomes 𝑓: 0.24 ( 35854 hom. )

Consequence

PHYH
NM_006214.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.962

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-13288291-G-T is Benign according to our data. Variant chr10-13288291-G-T is described in ClinVar as [Benign]. Clinvar id is 1226984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYH	NM_006214.4 link	c.678+69C>A		intron_variant	Intron 6 of 8	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.678+69C>A		intron_variant	Intron 6 of 8	1	NM_006214.4	ENSP00000263038.4		O14832-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41674

AN:

152050

Hom.:

5837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.243

AC:

283073

AN:

1165502

Hom.:

35854

AF XY:

0.247

AC XY:

146597

AN XY:

593806

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.271

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.274

AC:

41696

AN:

152170

Hom.:

5838

Cov.:

AF XY:

0.276

AC XY:

20507

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.334

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.301

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.241

Hom.:

6310

Bravo

AF:

0.272

Asia WGS

AF:

0.309

AC:

1074

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 11, 2018

GeneDx

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

-0.88

CADD

Benign

0.29

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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