10-13278111-GT-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006214.4(PHYH):c.*189del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (31990 hom., cov: 0)
  • Exomes 𝑓: 0.59 (61335 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.225

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-13278111-GT-G is Benign according to our data. Variant chr10-13278111-GT-G is described in ClinVar as [Benign]. Clinvar id is 299239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHYH	NM_006214.4	c.*189del		3_prime_UTR_variant	9/9	ENST00000263038.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHYH	ENST00000263038.9	c.*189del		3_prime_UTR_variant	9/9	1	NM_006214.4	P1
PHYH	ENST00000396913.6	c.*189del		3_prime_UTR_variant	8/8	5
PHYH	ENST00000396920.7	c.*189del		3_prime_UTR_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.648 AC: 97675 AN: 150672 Hom.: 31952 Cov.: 0

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.594

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.586 AC: 222731 AN: 379872 Hom.: 61335 Cov.: 0 AF XY: 0.589 AC XY: 119542 AN XY: 203000

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.648 AC: 97766 AN: 150788 Hom.: 31990 Cov.: 0 AF XY: 0.648 AC XY: 47695 AN XY: 73558

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.609

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Phytanic acid storage disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3839912; hg19: chr10-13320111;