Variant 19-3633461-C-CG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_012398.3(PIP5K1C):c.1979_1980insC(p.Ala661GlyfsTer81) variant causes a frameshift change. The variant allele was found at a frequency of 0.000351 in 1,501,830 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

PIP5K1C
NM_012398.3 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.014 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP5K1C	NM_012398.3 linkuse as main transcript	c.1979_1980insC	p.Ala661GlyfsTer81	frameshift_variant	17/18	ENST00000335312.8	NP_036530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8 linkuse as main transcript	c.1979_1980insC	p.Ala661GlyfsTer81	frameshift_variant	17/18	1	NM_012398.3	ENSP00000335333	P3	O60331-1
PIP5K1C	ENST00000679885.1 linkuse as main transcript	c.2057_2058insC	p.Ala687GlyfsTer81	frameshift_variant	18/19			ENSP00000504894	A1
PIP5K1C	ENST00000539785.5 linkuse as main transcript	c.1921-293_1921-292insC		intron_variant		2		ENSP00000445992	A1	O60331-4
PIP5K1C	ENST00000679828.1 linkuse as main transcript	c.1518_1519insC		3_prime_UTR_variant, NMD_transcript_variant	18/19			ENSP00000506175

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000357

AC:

482

AN:

1349628

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

227

AN XY:

661000

show subpopulations

Gnomad4 AFR exome

AF:

0.0000999

Gnomad4 AMR exome

AF:

0.000388

Gnomad4 ASJ exome

AF:

0.000100

Gnomad4 EAS exome

AF:

0.0000798

Gnomad4 SAS exome

AF:

0.000294

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.000372

Gnomad4 OTH exome

AF:

0.000470

GnomAD4 genome

AF:

0.000296

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000314

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 23, 2023

Frameshift variant predicted to result in protein truncation as the last 8 amino acids are replaced with 80 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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