10-13278111-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006214.4(PHYH):c.*189_*190insA 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 121 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHYH	NM_006214.4	c.*189_*190insA		3_prime_UTR_variant	9/9	ENST00000263038.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHYH	ENST00000263038.9	c.*189_*190insA		3_prime_UTR_variant	9/9	1	NM_006214.4	P1
PHYH	ENST00000396913.6	c.*189_*190insA		3_prime_UTR_variant	8/8	5
PHYH	ENST00000396920.7	c.*189_*190insA		3_prime_UTR_variant	9/9	5

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

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0229

Gnomad4 ASJ exome AF: 0.0285

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0485

Gnomad4 OTH exome AF: 0.0440

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

Gnomad4 AFR AF: 0.00768

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.0258

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3839912; hg19: chr10-13320111;