rs11133

Variant names:

• chr10-13278236-C-T
• rs11133
• NM_006214.4:c.*65G>A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.214
• Publications: 17 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=-0.82).
• BP6: Variant 10-13278236-C-T is Benign according to our data. Variant chr10-13278236-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006214.4. 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.*65G>A		3_prime_UTR	Exon 9 of 9	NP_006205.1	O14832-1
	PHYH	NM_001323082.2		c.*65G>A		3_prime_UTR	Exon 9 of 9	NP_001310011.1
	PHYH	NM_001323083.2		c.*65G>A		3_prime_UTR	Exon 7 of 7	NP_001310012.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYH	ENST00000263038.9	TSL:1 MANE Select	c.*65G>A		3_prime_UTR	Exon 9 of 9	ENSP00000263038.4	O14832-1
	PHYH	ENST00000858006.1		c.*65G>A		3_prime_UTR	Exon 9 of 9	ENSP00000528065.1
	PHYH	ENST00000943581.1		c.*65G>A		3_prime_UTR	Exon 9 of 9	ENSP00000613640.1

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

African (AFR) AF: 0.347 AC: 8106 AN: 23352

American (AMR) AF: 0.143 AC: 6261 AN: 43802

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 5287 AN: 22834

East Asian (EAS) AF: 0.201 AC: 7475 AN: 37182

South Asian (SAS) AF: 0.179 AC: 13446 AN: 75280

European-Finnish (FIN) AF: 0.295 AC: 15561 AN: 52760

Middle Eastern (MID) AF: 0.207 AC: 871 AN: 4210

European-Non Finnish (NFE) AF: 0.262 AC: 165870 AN: 632862

Other (OTH) AF: 0.247 AC: 10581 AN: 42752

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

African (AFR) AF: 0.348 AC: 14432 AN: 41418

American (AMR) AF: 0.168 AC: 2565 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3468

East Asian (EAS) AF: 0.190 AC: 979 AN: 5166

South Asian (SAS) AF: 0.178 AC: 858 AN: 4822

European-Finnish (FIN) AF: 0.298 AC: 3143 AN: 10540

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17677 AN: 67944

Other (OTH) AF: 0.235 AC: 497 AN: 2112

Alfa AF: 0.253 Hom.: 6594

Bravo AF: 0.264

Asia WGS AF: 0.202 AC: 702 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Phytanic acid storage disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.21
Mutation Taster		=100/0	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: rs11133; hg19: chr10-13320236;