Genetic Variant PIP5KL1:p.Glu316Lys (chr9-127922086-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001135219.2(PIP5KL1):c.946G>A(p.Glu316Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000601 in 1,551,296 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

PIP5KL1
NM_001135219.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Publications

0 publications found

Variant links:

Genes affected

PIP5KL1 (HGNC:28711): (phosphatidylinositol-4-phosphate 5-kinase like 1) PIP5KL1 is a phosphoinositide kinase-like protein that lacks intrinsic lipid kinase activity but associates with type I PIPKs (see PIP5K1A; MIM 603275) and may play a role in localization of PIPK activity (Chang et al., 2004 [PubMed 14701839]).[supplied by OMIM, Jun 2009]

PIP5KL1 links:

ENSG00000227218 (HGNC:):

ENSG00000227218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02700618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135219.2. 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
	PIP5KL1	NM_001135219.2	MANE Select	c.946G>A	p.Glu316Lys	missense	Exon 10 of 10	NP_001128691.1	Q5T9C9-1
	PIP5KL1	NM_173492.2		c.337G>A	p.Glu113Lys	missense	Exon 5 of 5	NP_775763.1	Q5T9C9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIP5KL1	ENST00000388747.9	TSL:5 MANE Select	c.946G>A	p.Glu316Lys	missense	Exon 10 of 10	ENSP00000373399.4	Q5T9C9-1
PIP5KL1	ENST00000300432.3	TSL:1	c.337G>A	p.Glu113Lys	missense	Exon 5 of 5	ENSP00000300432.3	Q5T9C9-2
PIP5KL1	ENST00000464759.5	TSL:3	n.384G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000260

AC:

AN:

161486

AF XY:

0.000230

show subpopulations

Gnomad AFR exome

AF:

0.000425

Gnomad AMR exome

AF:

0.0000374

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000525

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000645

AC:

902

AN:

1399056

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

451

AN XY:

690972

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

32070

American (AMR)

AF:

0.0000265

AC:

AN:

37798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25036

East Asian (EAS)

AF:

0.00

AC:

AN:

36600

South Asian (SAS)

AF:

0.0000748

AC:

AN:

80166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.000810

AC:

877

AN:

1082438

Other (OTH)

AF:

0.000207

AC:

AN:

58106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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

AF:

0.000204

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000236

AC:

ExAC

AF:

0.000155

AC:

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

0.094

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.015

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.80

M_CAP

Benign

0.0071

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.6

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.84

REVEL

Benign

0.083

Sift

Benign

0.55

Sift4G

Benign

0.43

Polyphen

0.033

Vest4

0.17

MVP

0.33

MPC

0.56

ClinPred

0.012

GERP RS

3.6

Varity_R

0.12

gMVP

0.45

Mutation Taster

=86/14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over