10-13288291-G-T

Variant names:

• chr10-13288291-G-T
• rs7900830
• NM_006214.4:c.678+69C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006214.4(PHYH):​c.678+69C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,317,672 control chromosomes in the GnomAD database, including 41,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5838 hom., cov: 33)
  • Exomes 𝑓: 0.24 (35854 hom.)
• Consequence: PHYH NM_006214.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.962
• Publications: 12 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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet
• phytanoyl-CoA hydroxylase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-13288291-G-T is Benign according to our data. Variant chr10-13288291-G-T is described in ClinVar as [Benign]. Clinvar id is 1226984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYH	NM_006214.4	c.678+69C>A		intron_variant	Intron 6 of 8	ENST00000263038.9	NP_006205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYH	ENST00000263038.9	c.678+69C>A		intron_variant	Intron 6 of 8	1	NM_006214.4	ENSP00000263038.4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41674 AN: 152050 Hom.: 5837 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.243 AC: 283073 AN: 1165502 Hom.: 35854 AF XY: 0.247 AC XY: 146597 AN XY: 593806

African (AFR) AF: 0.344 AC: 9432 AN: 27408

American (AMR) AF: 0.148 AC: 6547 AN: 44232

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 6747 AN: 24282

East Asian (EAS) AF: 0.269 AC: 10319 AN: 38426

South Asian (SAS) AF: 0.328 AC: 26145 AN: 79718

European-Finnish (FIN) AF: 0.271 AC: 14306 AN: 52790

Middle Eastern (MID) AF: 0.333 AC: 1216 AN: 3656

European-Non Finnish (NFE) AF: 0.232 AC: 195632 AN: 844326

Other (OTH) AF: 0.251 AC: 12729 AN: 50664

GnomAD4 genome AF: 0.274 AC: 41696 AN: 152170 Hom.: 5838 Cov.: 33 AF XY: 0.276 AC XY: 20507 AN XY: 74390

African (AFR) AF: 0.334 AC: 13856 AN: 41500

American (AMR) AF: 0.213 AC: 3253 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1556 AN: 5178

South Asian (SAS) AF: 0.345 AC: 1666 AN: 4830

European-Finnish (FIN) AF: 0.276 AC: 2922 AN: 10592

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16429 AN: 67998

Other (OTH) AF: 0.272 AC: 576 AN: 2114

Alfa AF: 0.245 Hom.: 9000

Bravo AF: 0.272

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.37
PhyloP100		-0.96
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: rs7900830; hg19: chr10-13330291; COSMIC: COSV107307662; COSMIC: COSV107307662;