5-103154707-TCA-CTC

Variant names:

• chr5-103154707-TCA-CTC
• NM_001276277.3:c.1255_1257delTCAinsCTC
• PPIP5K2 p.Ser419Leu

Variant summary

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

The NM_001276277.3(PPIP5K2):​c.1255_1257delTCAinsCTC​(p.Ser419Leu) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S419A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIP5K2 NM_001276277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

PPIP5K2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive 100

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276277.3. 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
	PPIP5K2	NM_001276277.3	MANE Select	c.1255_1257delTCAinsCTC	p.Ser419Leu	missense	N/A	NP_001263206.1	O43314-1
	PPIP5K2	NM_001281471.3		c.1255_1257delTCAinsCTC	p.Ser419Leu	missense	N/A	NP_001268400.1	A0A087WZV0
	PPIP5K2	NM_001345873.2		c.1255_1257delTCAinsCTC	p.Ser419Leu	missense	N/A	NP_001332802.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIP5K2	ENST00000358359.8	TSL:1 MANE Select	c.1255_1257delTCAinsCTC	p.Ser419Leu	missense	N/A	ENSP00000351126.3	O43314-1
	PPIP5K2	ENST00000414217.5	TSL:1	c.1255_1257delTCAinsCTC	p.Ser419Leu	missense	N/A	ENSP00000416016.1	O43314-2
	PPIP5K2	ENST00000613674.4	TSL:2	c.1255_1257delTCAinsCTC	p.Ser419Leu	missense	N/A	ENSP00000482907.1	A0A087WZV0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4

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: chr5-102490411;