Genetic Variant PHYKPL:p.Lys439Gln (chr5-178211959-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153373.4(PHYKPL):c.1315A>C(p.Lys439Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. K439E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PHYKPL
NM_153373.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.737

Publications

0 publications found

Variant links:

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

PHYKPL links:

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ACMG classification

Classification was made for transcript

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=0.07177374).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYKPL	NM_153373.4	MANE Select	c.1315A>C	p.Lys439Gln	missense	Exon 12 of 13	NP_699204.1	Q8IUZ5-1
PHYKPL	NM_001278346.1		c.1192A>C	p.Lys398Gln	missense	Exon 12 of 13	NP_001265275.1	Q8IUZ5
PHYKPL	NR_103508.1		n.1173A>C		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYKPL	ENST00000308158.10	TSL:1 MANE Select	c.1315A>C	p.Lys439Gln	missense	Exon 12 of 13	ENSP00000310978.5	Q8IUZ5-1
PHYKPL	ENST00000474052.5	TSL:1	n.*703A>C		non_coding_transcript_exon	Exon 9 of 10	ENSP00000423806.1	D6RCB8
PHYKPL	ENST00000494126.6	TSL:1	n.1956A>C		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.59

M_CAP

Benign

0.026

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.84

PhyloP100

0.74

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.28

REVEL

Benign

0.092

Sift

Benign

0.25

Sift4G

Benign

0.51

Polyphen

0.016

Vest4

0.32

MutPred

0.28

Loss of ubiquitination at K439 (P = 0.027)

MVP

0.66

MPC

0.088

ClinPred

0.055

GERP RS

1.4

Varity_R

0.099

gMVP

0.52

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over