15-43534882-A-G

Variant names:

• chr15-43534882-A-G
• rs150254952
• NM_001394395.1:c.4265T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001394395.1(PPIP5K1):​c.4265T>C​(p.Leu1422Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000729 in 1,613,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (0 hom.)
• Consequence: PPIP5K1 NM_001394395.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

Genes affected

PPIP5K1 (HGNC:29023): (diphosphoinositol pentakisphosphate kinase 1) This gene encodes a dual functional inositol kinase. The encoded enzyme converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate and diphosphoinositol pentakisphosphate to bis-diphosphoinositol tetrakisphosphate. This protein may be important for intracellular signaling pathways. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 15.[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02095431).
• BP6: Variant 15-43534882-A-G is Benign according to our data. Variant chr15-43534882-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2348819.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIP5K1	NM_001394395.1	c.4265T>C	p.Leu1422Pro	missense_variant	Exon 32 of 32	ENST00000420765.6	NP_001381324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIP5K1	ENST00000420765.6	c.4265T>C	p.Leu1422Pro	missense_variant	Exon 32 of 32	5	NM_001394395.1	ENSP00000400887.2

Frequencies

GnomAD3 genomes AF: 0.000382 AC: 58 AN: 151994 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000291 AC: 73 AN: 251200 AF XY: 0.000236

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000590

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000766 AC: 1119 AN: 1461778 Hom.: 0 Cov.: 31 AF XY: 0.000721 AC XY: 524 AN XY: 727192

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53406

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000951 AC: 1057 AN: 1111946

Other (OTH) AF: 0.000762 AC: 46 AN: 60396

GnomAD4 genome AF: 0.000382 AC: 58 AN: 151994 Hom.: 0 Cov.: 32 AF XY: 0.000418 AC XY: 31 AN XY: 74238

African (AFR) AF: 0.000218 AC: 9 AN: 41362

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000567 Hom.: 0

Bravo AF: 0.000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000931 AC: 8

ExAC AF: 0.000296 AC: 36

EpiCase AF: 0.000654

EpiControl AF: 0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 18, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	1.7
DANN	Benign	0.53
DEOGEN2	Benign	0.021	.;.;T;.;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.54	T;T;.;.;.;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.021	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N;.;.;.;N;.
PhyloP100		0.16
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.63	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.13	T;T;T;T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;B;B;B;B;.
Vest4		0.16
MVP		0.048
MPC		0.18
ClinPred		0.0042	T
GERP RS		-3.0
Varity_R		0.076
gMVP		0.18
Mutation Taster		=100/0	polymorphism

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

Publications

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Other links and lift over

dbSNP: rs150254952; hg19: chr15-43827080;