NM_001135219.2:c.931G>T

Variant names:

• chr9-127922101-C-A
• rs375350789
• NM_001135219.2:c.931G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135219.2(PIP5KL1):​c.931G>T​(p.Ala311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A311T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PIP5KL1 NM_001135219.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04796213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135219.2. 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
	PIP5KL1	NM_001135219.2	MANE Select	c.931G>T	p.Ala311Ser	missense	Exon 10 of 10	NP_001128691.1	Q5T9C9-1
	PIP5KL1	NM_173492.2		c.322G>T	p.Ala108Ser	missense	Exon 5 of 5	NP_775763.1	Q5T9C9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP5KL1	ENST00000388747.9	TSL:5 MANE Select	c.931G>T	p.Ala311Ser	missense	Exon 10 of 10	ENSP00000373399.4	Q5T9C9-1
	PIP5KL1	ENST00000300432.3	TSL:1	c.322G>T	p.Ala108Ser	missense	Exon 5 of 5	ENSP00000300432.3	Q5T9C9-2
	PIP5KL1	ENST00000464759.5	TSL:3	n.369G>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377412 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 677274

African (AFR) AF: 0.00 AC: 0 AN: 31474

American (AMR) AF: 0.00 AC: 0 AN: 36068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24288

East Asian (EAS) AF: 0.00 AC: 0 AN: 36042

South Asian (SAS) AF: 0.00 AC: 0 AN: 78690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069270

Other (OTH) AF: 0.00 AC: 0 AN: 57144

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N
PhyloP100		-0.14
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.027
Sift	Benign	0.36	T
Sift4G	Benign	0.47	T
Polyphen		0.010	B
Vest4		0.059
MutPred		0.38		Gain of phosphorylation at A311 (P = 0.0252)
MVP		0.095
MPC		0.37
ClinPred		0.088	T
GERP RS		-1.9
Varity_R		0.050
gMVP		0.25
Mutation Taster		=95/5	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: rs375350789; hg19: chr9-130684380;