rs377204058

Variant names:

• chr9-127922086-C-A
• rs377204058
• NM_001135219.2:c.946G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-127922086-C-A
• chr9-127922086-C-T

Variant summary

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

The NM_001135219.2(PIP5KL1):​c.946G>T​(p.Glu316*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIP5KL1 NM_001135219.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.946G>T	p.Glu316*	stop_gained	Exon 10 of 10	NP_001128691.1	Q5T9C9-1
	PIP5KL1	NM_173492.2		c.337G>T	p.Glu113*	stop_gained	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.946G>T	p.Glu316*	stop_gained	Exon 10 of 10	ENSP00000373399.4	Q5T9C9-1
	PIP5KL1	ENST00000300432.3	TSL:1	c.337G>T	p.Glu113*	stop_gained	Exon 5 of 5	ENSP00000300432.3	Q5T9C9-2
	PIP5KL1	ENST00000464759.5	TSL:3	n.384G>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399056 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690972

African (AFR) AF: 0.00 AC: 0 AN: 32070

American (AMR) AF: 0.00 AC: 0 AN: 37798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25036

East Asian (EAS) AF: 0.00 AC: 0 AN: 36600

South Asian (SAS) AF: 0.00 AC: 0 AN: 80166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082438

Other (OTH) AF: 0.00 AC: 0 AN: 58106

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.31
Eigen_PC	Benign	-0.0067
FATHMM_MKL	Benign	0.39	N
PhyloP100		1.6
Vest4		0.070
GERP RS		3.6
Mutation Taster		=14/186	disease causing

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: rs377204058; hg19: chr9-130684365;