Variant 19-3637458-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000589578.5(PIP5K1C):c.2076G>A(p.Pro692=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,535,700 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0047 ( 31 hom. )

Consequence

PIP5K1C
ENST00000589578.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-3637458-C-T is Benign according to our data. Variant chr19-3637458-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649003.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP5K1C	NM_012398.3 linkuse as main transcript	c.1920+1426G>A		intron_variant		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.1920+1426G>A		intron_variant		1	NM_012398.3	ENSP00000335333	P3	O60331-1

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

481

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00409

AC:

542

AN:

132648

Hom.:

AF XY:

0.00404

AC XY:

292

AN XY:

72334

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00985

Gnomad EAS exome

AF:

0.0000954

Gnomad SAS exome

AF:

0.00508

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00548

Gnomad OTH exome

AF:

0.00317

GnomAD4 exome

AF:

0.00472

AC:

6532

AN:

1383396

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

3289

AN XY:

682618

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00454

Gnomad4 FIN exome

AF:

0.000892

Gnomad4 NFE exome

AF:

0.00504

Gnomad4 OTH exome

AF:

0.00499

GnomAD4 genome

AF:

0.00316

AC:

481

AN:

152304

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00515

Hom.:

Bravo

AF:

0.00324

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PIP5K1C: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.053

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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