chr10-59234490-T-A

Variant names:

• chr10-59234490-T-A
• rs1840167291
• NM_032439.4:c.293T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032439.4(PHYHIPL):​c.293T>A​(p.Phe98Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,392,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. F98C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: PHYHIPL NM_032439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

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.293T>A	p.Phe98Tyr	missense	Exon 2 of 5	NP_115815.2	Q96FC7-1
	PHYHIPL	NM_001143774.2		c.215T>A	p.Phe72Tyr	missense	Exon 2 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.293T>A	p.Phe98Tyr	missense	Exon 2 of 5	ENSP00000362987.4	Q96FC7-1
	PHYHIPL	ENST00000373878.3	TSL:1	c.215T>A	p.Phe72Tyr	missense	Exon 2 of 5	ENSP00000362985.3	Q96FC7-2
	PHYHIPL	ENST00000486074.2	TSL:2	n.*234T>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000423634.1	Q96FC7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1392560 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 691228

African (AFR) AF: 0.00 AC: 0 AN: 28848

American (AMR) AF: 0.00 AC: 0 AN: 27806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23684

East Asian (EAS) AF: 0.00 AC: 0 AN: 36380

South Asian (SAS) AF: 0.00 AC: 0 AN: 75784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00000461 AC: 5 AN: 1085180

Other (OTH) AF: 0.0000175 AC: 1 AN: 57276

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	2.0	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.97	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.33		Gain of methylation at K93 (P = 0.0557)
MVP		0.79
MPC		1.5
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.42
Mutation Taster		=76/24	polymorphism

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: rs1840167291; hg19: chr10-60994250;