rs74868487

Variant names:

• chr5-103152479-G-A
• rs74868487
• NM_001276277.3:c.1029-169G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-103152479-G-A
• chr5-103152479-G-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.1029-169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 151,760 control chromosomes in the GnomAD database, including 336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.036 (336 hom., cov: 32)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.474
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-103152479-G-A is Benign according to our data. Variant chr5-103152479-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259606.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 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.1029-169G>A		intron	N/A	NP_001263206.1	O43314-1
	PPIP5K2	NM_001281471.3		c.1029-169G>A		intron	N/A	NP_001268400.1	A0A087WZV0
	PPIP5K2	NM_001345873.2		c.1029-169G>A		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.1029-169G>A		intron	N/A	ENSP00000351126.3	O43314-1
	PPIP5K2	ENST00000414217.5	TSL:1	c.1029-169G>A		intron	N/A	ENSP00000416016.1	O43314-2
	PPIP5K2	ENST00000613674.4	TSL:2	c.1029-169G>A		intron	N/A	ENSP00000482907.1	A0A087WZV0

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5509 AN: 151642 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000679

Gnomad OTH AF: 0.0226

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

GnomAD4 genome AF: 0.0364 AC: 5517 AN: 151760 Hom.: 336 Cov.: 32 AF XY: 0.0348 AC XY: 2583 AN XY: 74150

African (AFR) AF: 0.127 AC: 5244 AN: 41454

American (AMR) AF: 0.0111 AC: 169 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000679 AC: 46 AN: 67712

Other (OTH) AF: 0.0223 AC: 47 AN: 2104

Alfa AF: 0.0318 Hom.: 36

Bravo AF: 0.0414

Asia WGS AF: 0.00492 AC: 17 AN: 3466

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	-0.69
CADD	Benign	7.0
DANN	Benign	0.65
PhyloP100		0.47
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: rs74868487; hg19: chr5-102488183;