NM_153373.4:c.1189G>C

Variant names:

• chr5-178213087-C-G
• rs764115696
• NM_153373.4:c.1189G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153373.4(PHYKPL):​c.1189G>C​(p.Val397Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V397I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHYKPL NM_153373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

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]

PHYKPL Gene-Disease associations (from GenCC):

• phosphohydroxylysinuria

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17073008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153373.4. 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
	PHYKPL	NM_153373.4	MANE Select	c.1189G>C	p.Val397Leu	missense	Exon 11 of 13	NP_699204.1	Q8IUZ5-1
	PHYKPL	NM_001278346.1		c.1066G>C	p.Val356Leu	missense	Exon 11 of 13	NP_001265275.1	Q8IUZ5
	PHYKPL	NR_103508.1		n.1047G>C		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYKPL	ENST00000308158.10	TSL:1 MANE Select	c.1189G>C	p.Val397Leu	missense	Exon 11 of 13	ENSP00000310978.5	Q8IUZ5-1
	PHYKPL	ENST00000474052.5	TSL:1	n.*577G>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000423806.1	D6RCB8
	PHYKPL	ENST00000474052.5	TSL:1	n.*577G>C		3_prime_UTR	Exon 8 of 10	ENSP00000423806.1	D6RCB8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		3.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.054
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.047	D
Polyphen		0.017	B
Vest4		0.39
MutPred		0.59		Loss of catalytic residue at V397 (P = 0.0335)
MVP		0.15
MPC		0.091
ClinPred		0.86	D
GERP RS		1.7
Varity_R		0.33
gMVP		0.57
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs764115696; hg19: chr5-177640088;