10-59245068-G-A

Position:

• chr10-59245068-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032439.4(PHYHIPL):​c.608G>A​(p.Gly203Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PHYHIPL NM_032439.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89

Genes affected

PHYHIPL (HGNC:29378): (phytanoyl-CoA 2-hydroxylase interacting protein like) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14543235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHYHIPL	NM_032439.4	c.608G>A	p.Gly203Glu	missense_variant	5/5	ENST00000373880.9	NP_115815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHYHIPL	ENST00000373880.9	c.608G>A	p.Gly203Glu	missense_variant	5/5	1	NM_032439.4	ENSP00000362987.4
PHYHIPL	ENST00000373878.3	c.530G>A	p.Gly177Glu	missense_variant	5/5	1		ENSP00000362985.3
PHYHIPL	ENST00000486074.2	n.*549G>A		non_coding_transcript_exon_variant	6/6	2		ENSP00000423634.1
PHYHIPL	ENST00000486074.2	n.*549G>A		3_prime_UTR_variant	6/6	2		ENSP00000423634.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2024

The c.608G>A (p.G203E) alteration is located in exon 5 (coding exon 5) of the PHYHIPL gene. This alteration results from a G to A substitution at nucleotide position 608, causing the glycine (G) at amino acid position 203 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.23
Sift	Benign	0.031	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.011	B;B
Vest4		0.15
MutPred		0.42		Gain of solvent accessibility (P = 9e-04);.;
MVP		0.34
MPC		0.68
ClinPred		0.88	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-61004828;