chr10-13278111-GTT-G

Variant names:

• chr10-13278111-GTT-G
• rs3839912
• NM_006214.4:c.*188_*189delAA

Variant summary

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

The NM_006214.4(PHYH):​c.*188_*189delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 531,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• 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.*188_*189delAA		3_prime_UTR	Exon 9 of 9	NP_006205.1	O14832-1
	PHYH	NM_001323082.2		c.*188_*189delAA		3_prime_UTR	Exon 9 of 9	NP_001310011.1
	PHYH	NM_001323083.2		c.*188_*189delAA		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.*188_*189delAA		3_prime_UTR	Exon 9 of 9	ENSP00000263038.4	O14832-1
	PHYH	ENST00000858006.1		c.*188_*189delAA		3_prime_UTR	Exon 9 of 9	ENSP00000528065.1
	PHYH	ENST00000943581.1		c.*188_*189delAA		3_prime_UTR	Exon 9 of 9	ENSP00000613640.1

Frequencies

GnomAD3 genomes AF: 0.000206 AC: 31 AN: 150748 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000366

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00376

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000378 AC: 144 AN: 380974 Hom.: 0 AF XY: 0.000422 AC XY: 86 AN XY: 203610

African (AFR) AF: 0.000494 AC: 5 AN: 10114

American (AMR) AF: 0.0000576 AC: 1 AN: 17348

Ashkenazi Jewish (ASJ) AF: 0.00716 AC: 88 AN: 12290

East Asian (EAS) AF: 0.0000395 AC: 1 AN: 25308

South Asian (SAS) AF: 0.00 AC: 0 AN: 41334

European-Finnish (FIN) AF: 0.0000781 AC: 2 AN: 25610

Middle Eastern (MID) AF: 0.000597 AC: 1 AN: 1674

European-Non Finnish (NFE) AF: 0.000168 AC: 38 AN: 225910

Other (OTH) AF: 0.000374 AC: 8 AN: 21386

GnomAD4 genome AF: 0.000205 AC: 31 AN: 150864 Hom.: 0 Cov.: 0 AF XY: 0.000231 AC XY: 17 AN XY: 73612

African (AFR) AF: 0.000365 AC: 15 AN: 41130

American (AMR) AF: 0.0000664 AC: 1 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00376 AC: 13 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67698

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 1062

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

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;