chr9-127925936-C-A

Variant names:

• chr9-127925936-C-A
• rs766490893
• NM_001135219.2:c.694G>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.694G>T​(p.Ala232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,650 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. A232T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIP5KL1 NM_001135219.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• 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=0.048888534).

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.694G>T	p.Ala232Ser	missense	Exon 8 of 10	NP_001128691.1	Q5T9C9-1
	PIP5KL1	NM_173492.2		c.85G>T	p.Ala29Ser	missense	Exon 3 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.694G>T	p.Ala232Ser	missense	Exon 8 of 10	ENSP00000373399.4	Q5T9C9-1
	PIP5KL1	ENST00000300432.3	TSL:1	c.85G>T	p.Ala29Ser	missense	Exon 3 of 5	ENSP00000300432.3	Q5T9C9-2
	PIP5KL1	ENST00000464759.5	TSL:3	n.132G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461650 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111938

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.96	L
PhyloP100		1.9
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.040
Sift	Benign	0.47	T
Sift4G	Benign	0.53	T
Polyphen		0.26	B
Vest4		0.11
MutPred		0.25		Gain of disorder (P = 0.0169)
MVP		0.13
MPC		0.75
ClinPred		0.39	T
GERP RS		3.4
Varity_R		0.036
gMVP		0.25
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766490893; hg19: chr9-130688215;