chr10-13288402-T-C

Variant names:

• chr10-13288402-T-C
• rs473407
• NM_006214.4:c.636A>G

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.636A>G​(p.Thr212Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,613,770 control chromosomes in the GnomAD database, including 53,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6431 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47302 hom.)
• Consequence: PHYH NM_006214.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -3.16
• Publications: 22 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=-0.69).
• BP6: Variant 10-13288402-T-C is Benign according to our data. Variant chr10-13288402-T-C is described in ClinVar as Benign. ClinVar VariationId is 95349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 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.636A>G	p.Thr212Thr	synonymous	Exon 6 of 9	NP_006205.1	O14832-1
	PHYH	NM_001323082.2		c.642A>G	p.Thr214Thr	synonymous	Exon 6 of 9	NP_001310011.1
	PHYH	NM_001323084.2		c.342A>G	p.Thr114Thr	synonymous	Exon 5 of 8	NP_001310013.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYH	ENST00000263038.9	TSL:1 MANE Select	c.636A>G	p.Thr212Thr	synonymous	Exon 6 of 9	ENSP00000263038.4	O14832-1
	PHYH	ENST00000858006.1		c.636A>G	p.Thr212Thr	synonymous	Exon 6 of 9	ENSP00000528065.1
	PHYH	ENST00000943581.1		c.600A>G	p.Thr200Thr	synonymous	Exon 6 of 9	ENSP00000613640.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42556 AN: 152004 Hom.: 6413 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.233 AC: 58616 AN: 251216 AF XY: 0.228

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.0891

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.249 AC: 364641 AN: 1461648 Hom.: 47302 Cov.: 38 AF XY: 0.246 AC XY: 179092 AN XY: 727116

African (AFR) AF: 0.401 AC: 13425 AN: 33472

American (AMR) AF: 0.189 AC: 8435 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5904 AN: 26134

East Asian (EAS) AF: 0.146 AC: 5804 AN: 39698

South Asian (SAS) AF: 0.159 AC: 13702 AN: 86244

European-Finnish (FIN) AF: 0.280 AC: 14929 AN: 53406

Middle Eastern (MID) AF: 0.198 AC: 1123 AN: 5686

European-Non Finnish (NFE) AF: 0.258 AC: 286847 AN: 1111896

Other (OTH) AF: 0.240 AC: 14472 AN: 60390

GnomAD4 genome AF: 0.280 AC: 42622 AN: 152122 Hom.: 6431 Cov.: 32 AF XY: 0.277 AC XY: 20631 AN XY: 74376

African (AFR) AF: 0.393 AC: 16303 AN: 41470

American (AMR) AF: 0.192 AC: 2936 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.121 AC: 624 AN: 5162

South Asian (SAS) AF: 0.159 AC: 767 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2922 AN: 10592

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

European-Non Finnish (NFE) AF: 0.258 AC: 17537 AN: 67994

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

Alfa AF: 0.255 Hom.: 14922

Bravo AF: 0.278

Asia WGS AF: 0.165 AC: 571 AN: 3478

EpiCase AF: 0.247

EpiControl AF: 0.236

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	not provided (4)
-	-	3	Phytanic acid storage disease (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-3.2
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs473407; hg19: chr10-13330402; COSMIC: COSV53816118; COSMIC: COSV53816118;