Variant 19-3633194-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012398.3(PIP5K1C):c.2005-25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 760,796 control chromosomes in the GnomAD database, including 9,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1792 hom., cov: 33)

Exomes 𝑓: 0.15 ( 7752 hom. )

Consequence

PIP5K1C
NM_012398.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.248

Variant links:

Genes affected

PIP5K1C (HGNC:8996): (phosphatidylinositol-4-phosphate 5-kinase type 1 gamma) This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate, producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in endocytosis and cell migration. Mutations at this locus have been associated with lethal congenital contractural syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Sep 2010]

PIP5K1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-3633194-A-G is Benign according to our data. Variant chr19-3633194-A-G is described in ClinVar as [Benign]. Clinvar id is 1243421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PIP5K1C	NM_012398.3 linkuse as main transcript	c.2005-25T>C	intron_variant	ENST00000335312.8	NP_036530.1
PIP5K1C	NM_001195733.2 linkuse as main transcript	c.1921-25T>C	intron_variant		NP_001182662.1
PIP5K1C	XM_017026540.3 linkuse as main transcript	c.1972-25T>C	intron_variant		XP_016882029.1
PIP5K1C	XM_047438535.1 linkuse as main transcript	c.1888-25T>C	intron_variant		XP_047294491.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8 linkuse as main transcript	c.2005-25T>C	intron_variant	1	NM_012398.3	ENSP00000335333	P3	O60331-1
PIP5K1C	ENST00000539785.5 linkuse as main transcript	c.1921-25T>C	intron_variant	2		ENSP00000445992	A1	O60331-4
PIP5K1C	ENST00000679885.1 linkuse as main transcript	c.2083-25T>C	intron_variant			ENSP00000504894	A1
PIP5K1C	ENST00000679828.1 linkuse as main transcript	c.*1544-25T>C	intron_variant, NMD_transcript_variant			ENSP00000506175

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22631

AN:

151896

Hom.:

1792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.149

AC:

31660

AN:

212526

Hom.:

2676

AF XY:

0.146

AC XY:

16850

AN XY:

115370

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.152

AC:

92320

AN:

608782

Hom.:

7752

Cov.:

AF XY:

0.148

AC XY:

49113

AN XY:

330758

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.149

AC:

22632

AN:

152014

Hom.:

1792

Cov.:

AF XY:

0.147

AC XY:

10928

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.126

Hom.:

440

Bravo

AF:

0.153

Asia WGS

AF:

0.194

AC:

672

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.2

DANN

Benign

0.64

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

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