chr9-127925884-C-T

Variant names:

• chr9-127925884-C-T
• rs1831354682
• NM_001135219.2:c.746G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135219.2(PIP5KL1):​c.746G>A​(p.Gly249Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G249V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIP5KL1 NM_001135219.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

PIP5KL1 (HGNC:28711): (phosphatidylinositol-4-phosphate 5-kinase like 1) PIP5KL1 is a phosphoinositide kinase-like protein that lacks intrinsic lipid kinase activity but associates with type I PIPKs (see PIP5K1A; MIM 603275) and may play a role in localization of PIPK activity (Chang et al., 2004 [PubMed 14701839]).[supplied by OMIM, Jun 2009]

ENSG00000227218 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17571568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP5KL1	NM_001135219.2	c.746G>A	p.Gly249Asp	missense_variant	Exon 8 of 10	ENST00000388747.9	NP_001128691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP5KL1	ENST00000388747.9	c.746G>A	p.Gly249Asp	missense_variant	Exon 8 of 10	5	NM_001135219.2	ENSP00000373399.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000313 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		1.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.089
Sift	Benign	0.26	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.25	B;.
Vest4		0.21
MutPred		0.58		Gain of solvent accessibility (P = 0.1045);.;
MVP		0.31
MPC		0.60
ClinPred		0.89	D
GERP RS		2.4
Varity_R		0.23
gMVP		0.47
Mutation Taster		=59/41	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

Other links and lift over

dbSNP: rs1831354682; hg19: chr9-130688163;