10-13278111-GTT-GT

Variant names:

• chr10-13278111-GT-G
• rs3839912
• NM_006214.4:c.*189delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006214.4(PHYH):​c.*189delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (31990 hom., cov: 0)
  • Exomes 𝑓: 0.59 (61335 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.225
• Publications: 3 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 -16 ACMG points.

• BP6: Variant 10-13278111-GT-G is Benign according to our data. Variant chr10-13278111-GT-G is described in ClinVar as Benign. ClinVar VariationId is 299239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 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.*189delA		3_prime_UTR	Exon 9 of 9	NP_006205.1	O14832-1
	PHYH	NM_001323082.2		c.*189delA		3_prime_UTR	Exon 9 of 9	NP_001310011.1
	PHYH	NM_001323083.2		c.*189delA		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.*189delA		3_prime_UTR	Exon 9 of 9	ENSP00000263038.4	O14832-1
	PHYH	ENST00000858006.1		c.*189delA		3_prime_UTR	Exon 9 of 9	ENSP00000528065.1
	PHYH	ENST00000943581.1		c.*189delA		3_prime_UTR	Exon 9 of 9	ENSP00000613640.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 97675 AN: 150672 Hom.: 31952 Cov.: 0

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.594

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.586 AC: 222731 AN: 379872 Hom.: 61335 Cov.: 0 AF XY: 0.589 AC XY: 119542 AN XY: 203000

African (AFR) AF: 0.685 AC: 6917 AN: 10098

American (AMR) AF: 0.444 AC: 7664 AN: 17272

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 7070 AN: 12254

East Asian (EAS) AF: 0.483 AC: 12171 AN: 25220

South Asian (SAS) AF: 0.623 AC: 25692 AN: 41244

European-Finnish (FIN) AF: 0.669 AC: 17082 AN: 25538

Middle Eastern (MID) AF: 0.568 AC: 946 AN: 1666

European-Non Finnish (NFE) AF: 0.590 AC: 132806 AN: 225236

Other (OTH) AF: 0.580 AC: 12383 AN: 21344

GnomAD4 genome AF: 0.648 AC: 97766 AN: 150788 Hom.: 31990 Cov.: 0 AF XY: 0.648 AC XY: 47695 AN XY: 73558

African (AFR) AF: 0.729 AC: 29970 AN: 41114

American (AMR) AF: 0.499 AC: 7513 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2167 AN: 3456

East Asian (EAS) AF: 0.512 AC: 2612 AN: 5100

South Asian (SAS) AF: 0.659 AC: 3136 AN: 4758

European-Finnish (FIN) AF: 0.719 AC: 7439 AN: 10352

Middle Eastern (MID) AF: 0.597 AC: 173 AN: 290

European-Non Finnish (NFE) AF: 0.632 AC: 42779 AN: 67662

Other (OTH) AF: 0.609 AC: 1275 AN: 2092

Alfa AF: 0.538 Hom.: 1062

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
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: rs3839912; hg19: chr10-13320111; COSMIC: COSV53814539;