Variant rs142181517 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_153373.4(PHYKPL):c.1310A>T(p.Glu437Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,614,094 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 27 hom. )

Consequence

PHYKPL
NM_153373.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.33

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 5-178211964-T-A is Pathogenic according to our data. Variant chr5-178211964-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 39570.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.088317364). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 27 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHYKPL	NM_153373.4 linkuse as main transcript	c.1310A>T	p.Glu437Val	missense_variant	12/13	ENST00000308158.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHYKPL	ENST00000308158.10 linkuse as main transcript	c.1310A>T	p.Glu437Val	missense_variant	12/13	1	NM_153373.4	P1	Q8IUZ5-1

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

603

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00659

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00354

AC:

889

AN:

251406

Hom.:

AF XY:

0.00355

AC XY:

483

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.00616

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00551

AC:

8058

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00538

AC XY:

3911

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00307

Gnomad4 NFE exome

AF:

0.00670

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.00396

AC:

603

AN:

152240

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00659

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00554

Hom.:

Bravo

AF:

0.00374

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00347

AC:

421

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00611

EpiControl

AF:

0.00682

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Phosphohydroxylysinuria

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.024

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

M_CAP

Benign

0.055

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.99

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

REVEL

Pathogenic

0.85

Sift

Uncertain

0.011

Sift4G

Uncertain

0.054

Polyphen

0.17

Vest4

0.85

MVP

0.87

MPC

0.21

ClinPred

0.048

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over