10-13298236-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006214.4(PHYH):​c.85C>A​(p.Pro29Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHYH NM_006214.4 missense
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYH	NM_006214.4	c.85C>A	p.Pro29Thr	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>A	p.Pro29Thr	missense_variant	Exon 2 of 9	1	NM_006214.4	ENSP00000263038.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.47
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.20	T;T;.
Polyphen		0.73	P;P;.
Vest4		0.24
MutPred		0.63		Gain of catalytic residue at P29 (P = 0.0071);.;Gain of catalytic residue at P29 (P = 0.0071);
MVP		0.90
MPC		0.32
ClinPred		0.93	D
GERP RS		3.3
Varity_R		0.062
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;