10-13278111-GTT-GTTTTT

Variant names:

• chr10-13278111-G-GTTT
• rs3839912
• NM_006214.4:c.*187_*189dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006214.4(PHYH):​c.*187_*189dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*187_*189dupAAA		3_prime_UTR	Exon 9 of 9	NP_006205.1	O14832-1
	PHYH	NM_001323082.2		c.*187_*189dupAAA		3_prime_UTR	Exon 9 of 9	NP_001310011.1
	PHYH	NM_001323083.2		c.*187_*189dupAAA		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.*187_*189dupAAA		3_prime_UTR	Exon 9 of 9	ENSP00000263038.4	O14832-1
	PHYH	ENST00000858006.1		c.*187_*189dupAAA		3_prime_UTR	Exon 9 of 9	ENSP00000528065.1
	PHYH	ENST00000943581.1		c.*187_*189dupAAA		3_prime_UTR	Exon 9 of 9	ENSP00000613640.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000525 AC: 2 AN: 381114 Hom.: 0 Cov.: 0 AF XY: 0.00000491 AC XY: 1 AN XY: 203688

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10120

American (AMR) AF: 0.00 AC: 0 AN: 17354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12298

East Asian (EAS) AF: 0.00 AC: 0 AN: 25310

South Asian (SAS) AF: 0.00 AC: 0 AN: 41356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1674

European-Non Finnish (NFE) AF: 0.00000885 AC: 2 AN: 225982

Other (OTH) AF: 0.00 AC: 0 AN: 21400

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3839912; hg19: chr10-13320111;