10-59245429-C-G

Position:

• chr10-59245429-C-G

Variant summary

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

The NM_032439.4(PHYHIPL):​c.969C>G​(p.His323Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: PHYHIPL NM_032439.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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=0.22122797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHYHIPL	NM_032439.4	c.969C>G	p.His323Gln	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.969C>G	p.His323Gln	missense_variant	5/5	1	NM_032439.4	ENSP00000362987.4
PHYHIPL	ENST00000373878.3	c.891C>G	p.His297Gln	missense_variant	5/5	1		ENSP00000362985.3
PHYHIPL	ENST00000486074.2	n.*910C>G		non_coding_transcript_exon_variant	6/6	2		ENSP00000423634.1
PHYHIPL	ENST00000486074.2	n.*910C>G		3_prime_UTR_variant	6/6	2		ENSP00000423634.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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.969C>G (p.H323Q) alteration is located in exon 5 (coding exon 5) of the PHYHIPL gene. This alteration results from a C to G substitution at nucleotide position 969, causing the histidine (H) at amino acid position 323 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.18
Sift	Benign	0.27	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0030	B;B
Vest4		0.71
MutPred		0.34		Loss of sheet (P = 0.0084);.;
MVP		0.12
MPC		0.52
ClinPred		0.30	T
GERP RS		2.1
Varity_R		0.093
gMVP		0.50

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: chr10-61005189;