Genetic Variant PHYKPL:p.Ala386Ser (chr5-178214812-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153373.4(PHYKPL):c.1156G>T(p.Ala386Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PHYKPL
NM_153373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.488

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036584944).

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.1156G>T	p.Ala386Ser	missense	Exon 10 of 13	NP_699204.1	Q8IUZ5-1
PHYKPL	NM_001278346.1		c.1033G>T	p.Ala345Ser	missense	Exon 10 of 13	NP_001265275.1	Q8IUZ5
PHYKPL	NR_103508.1		n.1014G>T		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHYKPL	ENST00000308158.10	TSL:1 MANE Select	c.1156G>T	p.Ala386Ser	missense	Exon 10 of 13	ENSP00000310978.5	Q8IUZ5-1
PHYKPL	ENST00000474052.5	TSL:1	n.*544G>T		non_coding_transcript_exon	Exon 7 of 10	ENSP00000423806.1	D6RCB8
PHYKPL	ENST00000494126.6	TSL:1	n.1928G>T		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251430

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.095

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0050

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.30

PhyloP100

0.49

PrimateAI

Benign

0.23

PROVEAN

Benign

0.77

REVEL

Benign

0.015

Sift

Benign

0.84

Sift4G

Benign

0.79

Polyphen

0.0010

Vest4

0.13

MutPred

0.37

Gain of disorder (P = 0.033)

MVP

0.20

MPC

0.075

ClinPred

0.021

GERP RS

2.7

Varity_R

0.060

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over