chr5-178211964-T-C

Variant names:

• chr5-178211964-T-C
• rs142181517
• NM_153373.4:c.1310A>G

Variant summary

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

The NM_153373.4(PHYKPL):​c.1310A>G​(p.Glu437Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E437V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHYKPL NM_153373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYKPL	NM_153373.4	MANE Select	c.1310A>G	p.Glu437Gly	missense	Exon 12 of 13	NP_699204.1
	PHYKPL	NM_001278346.1		c.1187A>G	p.Glu396Gly	missense	Exon 12 of 13	NP_001265275.1
	PHYKPL	NR_103508.1		n.1168A>G		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHYKPL	ENST00000308158.10	TSL:1 MANE Select	c.1310A>G	p.Glu437Gly	missense	Exon 12 of 13	ENSP00000310978.5
	PHYKPL	ENST00000474052.5	TSL:1	n.*698A>G		non_coding_transcript_exon	Exon 9 of 10	ENSP00000423806.1
	PHYKPL	ENST00000494126.6	TSL:1	n.1951A>G		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.014
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.66
Sift	Benign	0.034	D
Sift4G	Uncertain	0.052	T
Polyphen		0.17	B
Vest4		0.68
MutPred		0.42		Loss of disorder (P = 0.07)
MVP		0.89
MPC		0.21
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.75
Mutation Taster		=81/19	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: rs142181517; hg19: chr5-177638965;