rs2452505

Variant names:

• chr10-59245484-G-C
• rs2452505
• NM_032439.4:c.1024G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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: 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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHIPL	NM_032439.4	MANE Select	c.1024G>C	p.Val342Leu	missense	Exon 5 of 5	NP_115815.2	Q96FC7-1
	PHYHIPL	NM_001143774.2		c.946G>C	p.Val316Leu	missense	Exon 5 of 5	NP_001137246.1	Q96FC7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYHIPL	ENST00000373880.9	TSL:1 MANE Select	c.1024G>C	p.Val342Leu	missense	Exon 5 of 5	ENSP00000362987.4	Q96FC7-1
	PHYHIPL	ENST00000373878.3	TSL:1	c.946G>C	p.Val316Leu	missense	Exon 5 of 5	ENSP00000362985.3	Q96FC7-2
	PHYHIPL	ENST00000486074.2	TSL:2	n.*965G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000423634.1	Q96FC7-3

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

GnomAD2 exomes AF: 0.820 AC: 205687 AN: 250832 AF XY: 0.819

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 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

African (AFR) AF: 0.515 AC: 17240 AN: 33476

American (AMR) AF: 0.868 AC: 38804 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 21616 AN: 26134

East Asian (EAS) AF: 0.851 AC: 33768 AN: 39696

South Asian (SAS) AF: 0.719 AC: 62046 AN: 86250

European-Finnish (FIN) AF: 0.896 AC: 47851 AN: 53414

Middle Eastern (MID) AF: 0.790 AC: 4557 AN: 5768

European-Non Finnish (NFE) AF: 0.843 AC: 937803 AN: 1111956

Other (OTH) AF: 0.816 AC: 49300 AN: 60396

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

African (AFR) AF: 0.531 AC: 22003 AN: 41440

American (AMR) AF: 0.855 AC: 13062 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2823 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4634 AN: 5170

South Asian (SAS) AF: 0.721 AC: 3472 AN: 4816

European-Finnish (FIN) AF: 0.896 AC: 9489 AN: 10594

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57551 AN: 68004

Other (OTH) AF: 0.791 AC: 1670 AN: 2112

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 v4.9

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
MetaRNN	Benign	0.0000022	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	N
PhyloP100		1.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2452505; hg19: chr10-61005244; COSMIC: COSV107323625; COSMIC: COSV107323625;