NM_006214.4:c.*189dupA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006214.4(PHYH):​c.*189dupA 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 0.032 (121 hom., cov: 0)
  • Exomes 𝑓: 0.044 (131 hom.)
• Consequence: PHYH NM_006214.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 10-13278111-G-GT is Benign according to our data. Variant chr10-13278111-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1223081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.032 (4831/150832) while in subpopulation NFE AF = 0.0437 (2958/67690). AF 95% confidence interval is 0.0424. There are 121 homozygotes in GnomAd4. There are 2464 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 121 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4834 AN: 150716 Hom.: 121 Cov.: 0

Gnomad AFR AF: 0.00771

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0261

GnomAD4 exome AF: 0.0435 AC: 16426 AN: 377276 Hom.: 131 Cov.: 0 AF XY: 0.0418 AC XY: 8439 AN XY: 201666

African (AFR) AF: 0.0116 AC: 117 AN: 10074

American (AMR) AF: 0.0229 AC: 389 AN: 17008

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 347 AN: 12174

East Asian (EAS) AF: 0.0187 AC: 465 AN: 24914

South Asian (SAS) AF: 0.0177 AC: 723 AN: 40954

European-Finnish (FIN) AF: 0.101 AC: 2572 AN: 25462

Middle Eastern (MID) AF: 0.0133 AC: 22 AN: 1660

European-Non Finnish (NFE) AF: 0.0485 AC: 10859 AN: 223868

Other (OTH) AF: 0.0440 AC: 932 AN: 21162

GnomAD4 genome AF: 0.0320 AC: 4831 AN: 150832 Hom.: 121 Cov.: 0 AF XY: 0.0335 AC XY: 2464 AN XY: 73596

African (AFR) AF: 0.00768 AC: 316 AN: 41126

American (AMR) AF: 0.0169 AC: 254 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3458

East Asian (EAS) AF: 0.0178 AC: 91 AN: 5106

South Asian (SAS) AF: 0.0118 AC: 56 AN: 4758

European-Finnish (FIN) AF: 0.0918 AC: 949 AN: 10340

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0437 AC: 2958 AN: 67690

Other (OTH) AF: 0.0258 AC: 54 AN: 2094

Alfa AF: 0.0451 Hom.: 1062

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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;