Variant chr19-3633117-C-A 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.*50G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 741,830 control chromosomes in the GnomAD database, including 8,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 1188 hom., cov: 33)

Exomes 𝑓: 0.12 ( 6991 hom. )

Consequence

PIP5K1C
NM_012398.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.200

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-3633117-C-A is Benign according to our data. Variant chr19-3633117-C-A is described in ClinVar as [Benign]. Clinvar id is 1262386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PIP5K1C	NM_012398.3 linkuse as main transcript	c.*50G>T	3_prime_UTR_variant	18/18	ENST00000335312.8	NP_036530.1
PIP5K1C	NM_001195733.2 linkuse as main transcript	c.*50G>T	3_prime_UTR_variant	17/17		NP_001182662.1
PIP5K1C	XM_017026540.3 linkuse as main transcript	c.*50G>T	3_prime_UTR_variant	17/17		XP_016882029.1
PIP5K1C	XM_047438535.1 linkuse as main transcript	c.*50G>T	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.*50G>T	3_prime_UTR_variant	18/18	1	NM_012398.3	ENSP00000335333	P3	O60331-1
PIP5K1C	ENST00000539785.5 linkuse as main transcript	c.*50G>T	3_prime_UTR_variant	17/17	2		ENSP00000445992	A1	O60331-4
PIP5K1C	ENST00000679885.1 linkuse as main transcript	c.*50G>T	3_prime_UTR_variant	19/19			ENSP00000504894	A1
PIP5K1C	ENST00000679828.1 linkuse as main transcript	c.*1596G>T	3_prime_UTR_variant, NMD_transcript_variant	19/19			ENSP00000506175

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14259

AN:

152046

Hom.:

1190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.0898

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0737

Gnomad OTH

AF:

0.0918

GnomAD3 exomes

AF:

0.146

AC:

26881

AN:

183668

Hom.:

3569

AF XY:

0.138

AC XY:

13889

AN XY:

100292

show subpopulations

Gnomad AFR exome

AF:

0.0374

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.0576

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0840

Gnomad NFE exome

AF:

0.0706

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.117

AC:

69089

AN:

589666

Hom.:

6991

Cov.:

AF XY:

0.117

AC XY:

37265

AN XY:

319728

show subpopulations

Gnomad4 AFR exome

AF:

0.0371

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.0578

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.0887

Gnomad4 NFE exome

AF:

0.0723

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0937

AC:

14258

AN:

152164

Hom.:

1188

Cov.:

AF XY:

0.100

AC XY:

7440

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0391

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.0562

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.0898

Gnomad4 NFE

AF:

0.0737

Gnomad4 OTH

AF:

0.0894

Alfa

AF:

0.0762

Hom.:

114

Bravo

AF:

0.105

Asia WGS

AF:

0.184

AC:

639

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.3

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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