19-3637461-CC-TT

Variant names:

• chr19-3637461-CC-TT
• ENST00000589578.5:c.2072_2073delGGinsAA
• PIP5K1C p.Arg691Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001300849.2(PIP5K1C):​c.2072_2073delGGinsAA​(p.Arg691Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R691L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PIP5K1C NM_001300849.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300849.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP5K1C	NM_012398.3	MANE Select	c.1920+1422_1920+1423delGGinsAA		intron	N/A	NP_036530.1	O60331-1
	PIP5K1C	NM_001300849.2		c.2072_2073delGGinsAA	p.Arg691Gln	missense	N/A	NP_001287778.1	O60331-3
	PIP5K1C	NM_001195733.2		c.1920+1422_1920+1423delGGinsAA		intron	N/A	NP_001182662.1	O60331-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP5K1C	ENST00000589578.5	TSL:1	c.2072_2073delGGinsAA	p.Arg691Gln	missense	N/A	ENSP00000466363.1	O60331-3
	PIP5K1C	ENST00000537021.1	TSL:1	c.*362_*363delGGinsAA		3_prime_UTR	Exon 17 of 17	ENSP00000444779.1	O60331-2
	PIP5K1C	ENST00000335312.8	TSL:1 MANE Select	c.1920+1422_1920+1423delGGinsAA		intron	N/A	ENSP00000335333.3	O60331-1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.072

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-3637459;