5-103152867-T-C

Variant names:

• chr5-103152867-T-C
• rs27896
• NM_001276277.3:c.1130+118T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001276277.3(PPIP5K2):​c.1130+118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 619,890 control chromosomes in the GnomAD database, including 25,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5060 hom., cov: 32)
  • Exomes 𝑓: 0.28 (19992 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130
• Publications: 15 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-103152867-T-C is Benign according to our data. Variant chr5-103152867-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

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.1130+118T>C		intron	N/A	NP_001263206.1	O43314-1
	PPIP5K2	NM_001281471.3		c.1130+118T>C		intron	N/A	NP_001268400.1	A0A087WZV0
	PPIP5K2	NM_001345873.2		c.1130+118T>C		intron	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.1130+118T>C		intron	N/A	ENSP00000351126.3	O43314-1
	PPIP5K2	ENST00000414217.5	TSL:1	c.1130+118T>C		intron	N/A	ENSP00000416016.1	O43314-2
	PPIP5K2	ENST00000613674.4	TSL:2	c.1130+118T>C		intron	N/A	ENSP00000482907.1	A0A087WZV0

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36097 AN: 151654 Hom.: 5063 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.280 AC: 130936 AN: 468118 Hom.: 19992 AF XY: 0.274 AC XY: 67812 AN XY: 247754

African (AFR) AF: 0.0987 AC: 1104 AN: 11184

American (AMR) AF: 0.202 AC: 2956 AN: 14604

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 2831 AN: 12882

East Asian (EAS) AF: 0.452 AC: 12733 AN: 28180

South Asian (SAS) AF: 0.140 AC: 5252 AN: 37574

European-Finnish (FIN) AF: 0.325 AC: 13041 AN: 40068

Middle Eastern (MID) AF: 0.188 AC: 618 AN: 3282

European-Non Finnish (NFE) AF: 0.291 AC: 85665 AN: 294712

Other (OTH) AF: 0.263 AC: 6736 AN: 25632

GnomAD4 genome AF: 0.238 AC: 36111 AN: 151772 Hom.: 5060 Cov.: 32 AF XY: 0.237 AC XY: 17596 AN XY: 74170

African (AFR) AF: 0.0991 AC: 4114 AN: 41526

American (AMR) AF: 0.229 AC: 3494 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3464

East Asian (EAS) AF: 0.449 AC: 2314 AN: 5150

South Asian (SAS) AF: 0.140 AC: 677 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3421 AN: 10570

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20376 AN: 67686

Other (OTH) AF: 0.233 AC: 490 AN: 2102

Alfa AF: 0.270 Hom.: 5982

Bravo AF: 0.226

Asia WGS AF: 0.256 AC: 884 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.5
DANN	Benign	0.59
PhyloP100		-0.013
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: rs27896; hg19: chr5-102488571; COSMIC: COSV58603996; COSMIC: COSV58603996;