19-3633275-G-C

Position:

• chr19-3633275-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012398.3(PIP5K1C):​c.2005-106C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 680,774 control chromosomes in the GnomAD database, including 92,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17939 hom., cov: 33)
  • Exomes 𝑓: 0.50 (74398 hom.)
• Consequence: PIP5K1C NM_012398.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-3633275-G-C is Benign according to our data. Variant chr19-3633275-G-C is described in ClinVar as [Benign]. Clinvar id is 1245619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP5K1C	NM_012398.3	c.2005-106C>G		intron_variant		ENST00000335312.8	NP_036530.1
PIP5K1C	NM_001195733.2	c.1921-106C>G		intron_variant			NP_001182662.1
PIP5K1C	XM_017026540.3	c.1972-106C>G		intron_variant			XP_016882029.1
PIP5K1C	XM_047438535.1	c.1888-106C>G		intron_variant			XP_047294491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8	c.2005-106C>G		intron_variant		1	NM_012398.3	ENSP00000335333	P3
PIP5K1C	ENST00000539785.5	c.1921-106C>G		intron_variant		2		ENSP00000445992	A1
PIP5K1C	ENST00000679885.1	c.2083-106C>G		intron_variant				ENSP00000504894	A1
PIP5K1C	ENST00000679828.1	c.*1544-106C>G		intron_variant, NMD_transcript_variant				ENSP00000506175

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69664 AN: 151962 Hom.: 17942 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.504 AC: 266649 AN: 528694 Hom.: 74398 Cov.: 6 AF XY: 0.499 AC XY: 140105 AN XY: 280962

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.458 AC: 69669 AN: 152080 Hom.: 17939 Cov.: 33 AF XY: 0.452 AC XY: 33597 AN XY: 74358

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.0700

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.490

Alfa AF: 0.533 Hom.: 2820

Bravo AF: 0.436

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs542690; hg19: chr19-3633273; COSMIC: COSV58951956; COSMIC: COSV58951956;