Genetic Variant PIP5K1C:c.*194G>A (chr19-3632973-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012398.3(PIP5K1C):c.*194G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000063 in 524,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

PIP5K1C
NM_012398.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.500

Publications

4 publications found

Variant links:

Genes affected

PIP5K1C (HGNC:8996): (phosphatidylinositol-4-phosphate 5-kinase type 1 gamma) This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate, producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in endocytosis and cell migration. Mutations at this locus have been associated with lethal congenital contractural syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Sep 2010]

PIP5K1C Gene-Disease associations (from GenCC):

lethal congenital contracture syndrome 3
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

PIP5K1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012398.3. 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
	PIP5K1C	NM_012398.3	MANE Select	c.*194G>A		3_prime_UTR	Exon 18 of 18	NP_036530.1	O60331-1
	PIP5K1C	NM_001195733.2		c.*194G>A		3_prime_UTR	Exon 17 of 17	NP_001182662.1	O60331-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIP5K1C	ENST00000335312.8	TSL:1 MANE Select	c.*194G>A	3_prime_UTR	Exon 18 of 18	ENSP00000335333.3	O60331-1
PIP5K1C	ENST00000876625.1		c.*194G>A	3_prime_UTR	Exon 19 of 19	ENSP00000546684.1
PIP5K1C	ENST00000967141.1		c.*194G>A	3_prime_UTR	Exon 18 of 18	ENSP00000637200.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

372108

Hom.:

Cov.:

AF XY:

0.0000512

AC XY:

AN XY:

195476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8180

American (AMR)

AF:

0.0000709

AC:

AN:

14108

Ashkenazi Jewish (ASJ)

AF:

0.0000882

AC:

AN:

11336

East Asian (EAS)

AF:

0.0000395

AC:

AN:

25332

South Asian (SAS)

AF:

0.00

AC:

AN:

33074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28246

Middle Eastern (MID)

AF:

0.000600

AC:

AN:

1668

European-Non Finnish (NFE)

AF:

0.0000834

AC:

AN:

227842

Other (OTH)

AF:

0.0000448

AC:

AN:

22322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41472

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.96

PhyloP100

-0.50

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over