chr10-13298236-G-C

Variant names:

• chr10-13298236-G-C
• NM_006214.4:c.85C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001323080.2(PHYH):​c.-216C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHYH NM_001323080.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3024907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYH	NM_006214.4	c.85C>G	p.Pro29Ala	missense_variant	Exon 2 of 9	ENST00000263038.9	NP_006205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYH	ENST00000263038.9	c.85C>G	p.Pro29Ala	missense_variant	Exon 2 of 9	1	NM_006214.4	ENSP00000263038.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446726 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 720722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Uncertain	0.46	T;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.18	T;T;.
Polyphen		0.12	B;B;.
Vest4		0.25
MutPred		0.55		Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);
MVP		0.85
MPC		0.15
ClinPred		0.30	T
GERP RS		3.3
Varity_R		0.042
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-13340236;