5-103147030-C-T

Variant names:

• chr5-103147030-C-T
• rs26521
• NM_001276277.3:c.642+349C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001276277.3(PPIP5K2):​c.642+349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,694 control chromosomes in the GnomAD database, including 2,445 homozygotes. 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: 𝑓 0.16 (2445 hom., cov: 32)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 13 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 100

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIP5K2	NM_001276277.3	c.642+349C>T		intron_variant	Intron 6 of 30	ENST00000358359.8	NP_001263206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.642+349C>T		intron_variant	Intron 6 of 30	1	NM_001276277.3	ENSP00000351126.3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24002 AN: 151574 Hom.: 2437 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.158 AC: 24004 AN: 151694 Hom.: 2445 Cov.: 32 AF XY: 0.161 AC XY: 11921 AN XY: 74118

African (AFR) AF: 0.0405 AC: 1679 AN: 41484

American (AMR) AF: 0.247 AC: 3761 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3460

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5164

South Asian (SAS) AF: 0.278 AC: 1338 AN: 4814

European-Finnish (FIN) AF: 0.153 AC: 1615 AN: 10526

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13124 AN: 67688

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.158 Hom.: 1827

Bravo AF: 0.161

Asia WGS AF: 0.264 AC: 915 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs26521; hg19: chr5-102482734;