chr17-8888215-GGA-ACT

Variant names:

• chr17-8888215-GGA-ACT
• NM_001142633.3:c.1570_1572delTCCinsAGT
• PIK3R5 p.525

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001142633.3(PIK3R5):​c.1570_1572delTCCinsAGT​(p.525) variant causes a synonymous change involving the alteration of a 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. Synonymous variant affecting the same amino acid position (i.e. S524S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PIK3R5 NM_001142633.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.40
• Publications: 0 publications found

Genes affected

PIK3R5 (HGNC:30035): (phosphoinositide-3-kinase regulatory subunit 5) Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. This protein recruits the catalytic subunit from the cytosol to the plasma membrane through high-affinity interaction with G-beta-gamma proteins. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found. [provided by RefSeq, Oct 2011]

PIK3R5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• ataxia with oculomotor apraxia type 3

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000297004 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142633.3. 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
	PIK3R5	NM_001142633.3	MANE Select	c.1570_1572delTCCinsAGT	p.525	synonymous	N/A	NP_001136105.1	L7RT34
	PIK3R5	NM_014308.4		c.1570_1572delTCCinsAGT	p.525	synonymous	N/A	NP_055123.2	Q8WYR1-1
	PIK3R5	NM_001388396.1		c.1570_1572delTCCinsAGT	p.525	synonymous	N/A	NP_001375325.1	J3KSW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R5	ENST00000447110.6	TSL:5 MANE Select	c.1570_1572delTCCinsAGT	p.525	synonymous	N/A	ENSP00000392812.1	Q8WYR1-1
	PIK3R5	ENST00000581552.5	TSL:1	c.1570_1572delTCCinsAGT	p.525	synonymous	N/A	ENSP00000462433.1	Q8WYR1-1
	PIK3R5	ENST00000623421.3	TSL:1	c.412_414delTCCinsAGT	p.139	synonymous	N/A	ENSP00000485280.1	Q8WYR1-2

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		9.4

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: chr17-8791532;