rs142385761

Variant names:

• chr5-178214869-T-A
• rs142385761
• NM_153373.4:c.1099A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-178214869-T-A
• chr5-178214869-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153373.4(PHYKPL):​c.1099A>T​(p.Ile367Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,386 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PHYKPL NM_153373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

Genes affected

PHYKPL (HGNC:28249): (5-phosphohydroxy-L-lysine phospho-lyase) This is a nuclear gene encoding a mitochondrial enzyme that catalyzes the conversion of 5-phosphonooxy-L-lysine to ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde. Mutations in this gene may cause phosphohydroxylysinuria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHYKPL	NM_153373.4	c.1099A>T	p.Ile367Phe	missense_variant	Exon 10 of 13	ENST00000308158.10	NP_699204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHYKPL	ENST00000308158.10	c.1099A>T	p.Ile367Phe	missense_variant	Exon 10 of 13	1	NM_153373.4	ENSP00000310978.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461386 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727018

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.10	T
Polyphen		0.92	P
Vest4		0.64
MutPred		0.70		Loss of stability (P = 0.1077);
MVP		0.95
MPC		0.46
ClinPred		0.96	D
GERP RS		-0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.82

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: rs142385761; hg19: chr5-177641870;