Variant 19-3633161-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_012398.3(PIP5K1C):c.*6A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 767,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

PIP5K1C
NM_012398.3 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.09

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-3633161-T-C is Benign according to our data. Variant chr19-3633161-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052505.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PIP5K1C	NM_012398.3 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	18/18	ENST00000335312.8	NP_036530.1
PIP5K1C	NM_001195733.2 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	17/17		NP_001182662.1
PIP5K1C	XM_017026540.3 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	17/17		XP_016882029.1
PIP5K1C	XM_047438535.1 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	16/16		XP_047294491.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	18/18	1	NM_012398.3	ENSP00000335333	P3	O60331-1
PIP5K1C	ENST00000539785.5 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	17/17	2		ENSP00000445992	A1	O60331-4
PIP5K1C	ENST00000679885.1 linkuse as main transcript	c.*6A>G	3_prime_UTR_variant	19/19			ENSP00000504894	A1
PIP5K1C	ENST00000679828.1 linkuse as main transcript	c.*1552A>G	3_prime_UTR_variant, NMD_transcript_variant	19/19			ENSP00000506175

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000450

AC:

AN:

222092

Hom.:

AF XY:

0.0000579

AC XY:

AN XY:

120796

show subpopulations

Gnomad AFR exome

AF:

0.0000750

Gnomad AMR exome

AF:

0.0000312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000213

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000204

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000553

AC:

AN:

615018

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

334346

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000340

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000871

Gnomad4 OTH exome

AF:

0.0000307

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.0000831

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PIP5K1C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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