10-13278236-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006214.4(PHYH):c.*65G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,086,974 control chromosomes in the GnomAD database, including 35,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5728 hom., cov: 32)
  • Exomes 𝑓: 0.25 (30181 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.214

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-13278236-C-T is Benign according to our data. Variant chr10-13278236-C-T is described in ClinVar as [Benign]. Clinvar id is 299240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHYH	NM_006214.4	c.*65G>A		3_prime_UTR_variant	9/9	ENST00000263038.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHYH	ENST00000263038.9	c.*65G>A		3_prime_UTR_variant	9/9	1	NM_006214.4	P1
PHYH	ENST00000396913.6	c.*65G>A		3_prime_UTR_variant	8/8	5
PHYH	ENST00000396920.7	c.*65G>A		3_prime_UTR_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41117 AN: 151820 Hom.: 5718 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.250 AC: 233458 AN: 935034 Hom.: 30181 Cov.: 13 AF XY: 0.247 AC XY: 120568 AN XY: 487816

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.271 AC: 41180 AN: 151940 Hom.: 5728 Cov.: 32 AF XY: 0.268 AC XY: 19874 AN XY: 74252

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.235

Alfa AF: 0.252 Hom.: 4790

Bravo AF: 0.264

Asia WGS AF: 0.202 AC: 702 AN: 3472

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

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.1
Dann	Benign	0.67

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: rs11133; hg19: chr10-13320236;