19-3633194-A-T

Variant names:

• chr19-3633194-A-T
• rs542462
• NM_012398.3:c.2005-25T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012398.3(PIP5K1C):​c.2005-25T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIP5K1C NM_012398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP5K1C	NM_012398.3	c.2005-25T>A		intron_variant	Intron 17 of 17	ENST00000335312.8	NP_036530.1
PIP5K1C	NM_001195733.2	c.1921-25T>A		intron_variant	Intron 16 of 16		NP_001182662.1
PIP5K1C	XM_017026540.3	c.1972-25T>A		intron_variant	Intron 16 of 16		XP_016882029.1
PIP5K1C	XM_047438535.1	c.1888-25T>A		intron_variant	Intron 15 of 15		XP_047294491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8	c.2005-25T>A		intron_variant	Intron 17 of 17	1	NM_012398.3	ENSP00000335333.3
PIP5K1C	ENST00000679885.1	c.2083-25T>A		intron_variant	Intron 18 of 18			ENSP00000504894.1
PIP5K1C	ENST00000539785.5	c.1921-25T>A		intron_variant	Intron 16 of 16	2		ENSP00000445992.1
PIP5K1C	ENST00000679828.1	n.*1544-25T>A		intron_variant	Intron 18 of 18			ENSP00000506175.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 609892 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 331418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs542462; hg19: chr19-3633192;