Variant 10-13278254-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006214.4(PHYH):c.*47G>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 0.000438 in 1,240,320 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

PHYH
NM_006214.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.594

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-13278254-C-T is Benign according to our data. Variant chr10-13278254-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 299241.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00179 (272/152248) while in subpopulation AFR AF= 0.00606 (252/41554). AF 95% confidence interval is 0.00545. There are 3 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHYH	NM_006214.4 linkuse as main transcript	c.*47G>A		3_prime_UTR_variant	9/9	ENST00000263038.9	NP_006205.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHYH	ENST00000263038.9 linkuse as main transcript	c.*47G>A	3_prime_UTR_variant	9/9	1	NM_006214.4	ENSP00000263038	P1	O14832-1
PHYH	ENST00000396913.6 linkuse as main transcript	c.*47G>A	3_prime_UTR_variant	8/8	5		ENSP00000380121		O14832-2
PHYH	ENST00000396920.7 linkuse as main transcript	c.*47G>A	3_prime_UTR_variant	9/9	5		ENSP00000380126

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000415

AC:

104

AN:

250564

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00507

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000249

AC:

271

AN:

1088072

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

105

AN XY:

559120

show subpopulations

Gnomad4 AFR exome

AF:

0.00545

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.000292

GnomAD4 genome

AF:

0.00179

AC:

272

AN:

152248

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00606

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00180

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Phytanic acid storage disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

DANN

Benign

0.39

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