rs2452505

Positions:

• chr10-59245484-G-C
• chr10-59245484-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032439.4(PHYHIPL):​c.1024G>C​(p.Val342Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,613,906 control chromosomes in the GnomAD database, including 552,085 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.76 (45762 hom., cov: 32)
  • Exomes 𝑓: 0.83 (506323 hom.)
• Consequence: PHYHIPL NM_032439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1492385E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHYHIPL	NM_032439.4	c.1024G>C	p.Val342Leu	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.1024G>C	p.Val342Leu	missense_variant	5/5	1	NM_032439.4	ENSP00000362987.4
PHYHIPL	ENST00000373878.3	c.946G>C	p.Val316Leu	missense_variant	5/5	1		ENSP00000362985.3
PHYHIPL	ENST00000486074.2	n.*965G>C		non_coding_transcript_exon_variant	6/6	2		ENSP00000423634.1
PHYHIPL	ENST00000486074.2	n.*965G>C		3_prime_UTR_variant	6/6	2		ENSP00000423634.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115714 AN: 151980 Hom.: 45755 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.791

GnomAD3 exomes AF: 0.820 AC: 205687 AN: 250832 Hom.: 85505 AF XY: 0.819 AC XY: 110984 AN XY: 135558

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.867

Gnomad ASJ exome AF: 0.826

Gnomad EAS exome AF: 0.912

Gnomad SAS exome AF: 0.718

Gnomad FIN exome AF: 0.895

Gnomad NFE exome AF: 0.846

Gnomad OTH exome AF: 0.834

GnomAD4 exome AF: 0.830 AC: 1212985 AN: 1461808 Hom.: 506323 Cov.: 61 AF XY: 0.827 AC XY: 601679 AN XY: 727204

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.868

Gnomad4 ASJ exome AF: 0.827

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.843

Gnomad4 OTH exome AF: 0.816

GnomAD4 genome AF: 0.761 AC: 115751 AN: 152098 Hom.: 45762 Cov.: 32 AF XY: 0.765 AC XY: 56912 AN XY: 74364

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.791

Alfa AF: 0.831 Hom.: 39877

Bravo AF: 0.749

TwinsUK AF: 0.844 AC: 3129

ALSPAC AF: 0.831 AC: 3202

ESP6500AA AF: 0.539 AC: 2376

ESP6500EA AF: 0.842 AC: 7239

ExAC AF: 0.810 AC: 98395

Asia WGS AF: 0.779 AC: 2705 AN: 3478

EpiCase AF: 0.841

EpiControl AF: 0.847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.035	T;T
MetaRNN	Benign	0.0000021	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	N;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.63	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.033
MutPred		0.26		Gain of glycosylation at S341 (P = 0.1116);.;
MPC		0.50
ClinPred		0.0015	T
GERP RS		5.6
Varity_R		0.035
gMVP		0.094

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

LitVar

Other links and lift over

dbSNP: rs2452505; hg19: chr10-61005244;