rs1747682

Variant names:

• chr10-13295588-G-A
• rs1747682
• NM_006214.4:c.153C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001323084.2(PHYH):​c.-148C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,313,394 control chromosomes in the GnomAD database, including 648,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71952 hom., cov: 31)
  • Exomes 𝑓: 1.0 (576610 hom.)
• Consequence: PHYH NM_001323084.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.222
• Publications: 23 publications found

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, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
• phytanoyl-CoA hydroxylase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-13295588-G-A is Benign according to our data. Variant chr10-13295588-G-A is described in ClinVar as Benign. ClinVar VariationId is 129891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323084.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYH	NM_006214.4	MANE Select	c.153C>T	p.Asn51Asn	synonymous	Exon 3 of 9	NP_006205.1	O14832-1
	PHYH	NM_001323084.2		c.-148C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001310013.1
	PHYH	NM_001037537.2		c.-148C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001032626.1	O14832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYH	ENST00000263038.9	TSL:1 MANE Select	c.153C>T	p.Asn51Asn	synonymous	Exon 3 of 9	ENSP00000263038.4	O14832-1
	PHYH	ENST00000396913.6	TSL:5	c.-148C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000380121.2	O14832-2
	PHYH	ENST00000453759.6	TSL:5	c.-148C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	ENSP00000412525.2	C9IYS5

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147752 AN: 152128 Hom.: 71907 Cov.: 31

Gnomad AFR AF: 0.900

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.977

GnomAD2 exomes AF: 0.992 AC: 249233 AN: 251144 AF XY: 0.994

Gnomad AFR exome AF: 0.900

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.996 AC: 1156972 AN: 1161148 Hom.: 576610 Cov.: 17 AF XY: 0.997 AC XY: 590830 AN XY: 592650

African (AFR) AF: 0.888 AC: 24916 AN: 28052

American (AMR) AF: 0.996 AC: 44163 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 24176 AN: 24272

East Asian (EAS) AF: 1.00 AC: 38328 AN: 38328

South Asian (SAS) AF: 0.999 AC: 79945 AN: 80028

European-Finnish (FIN) AF: 1.00 AC: 53171 AN: 53172

Middle Eastern (MID) AF: 0.994 AC: 5086 AN: 5118

European-Non Finnish (NFE) AF: 1.00 AC: 837254 AN: 837464

Other (OTH) AF: 0.992 AC: 49933 AN: 50360

GnomAD4 genome AF: 0.971 AC: 147856 AN: 152246 Hom.: 71952 Cov.: 31 AF XY: 0.972 AC XY: 72357 AN XY: 74440

African (AFR) AF: 0.900 AC: 37357 AN: 41504

American (AMR) AF: 0.991 AC: 15138 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3455 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.999 AC: 4823 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68016 AN: 68042

Other (OTH) AF: 0.977 AC: 2067 AN: 2116

Alfa AF: 0.991 Hom.: 94636

Bravo AF: 0.967

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	3	Phytanic acid storage disease (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.8
DANN	Benign	0.61
PhyloP100		0.22
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1747682; hg19: chr10-13337588; COSMIC: COSV108080965; COSMIC: COSV108080965;