Genetic Variant ENST00000589578.5:c.2022C>T (chr19-3637512-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000589578.5(PIP5K1C):c.2022C>T(p.Pro674Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,535,596 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00071 ( 6 hom. )

Consequence

PIP5K1C
ENST00000589578.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0170

Publications

0 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-3637512-G-A is Benign according to our data. Variant chr19-3637512-G-A is described in ClinVar as Benign. ClinVar VariationId is 2649004.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000589578.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIP5K1C	NM_012398.3	MANE Select	c.1920+1372C>T		intron	N/A	NP_036530.1	O60331-1
PIP5K1C	NM_001300849.2		c.2022C>T	p.Pro674Pro	synonymous	Exon 17 of 17	NP_001287778.1	O60331-3
PIP5K1C	NM_001195733.2		c.1920+1372C>T		intron	N/A	NP_001182662.1	O60331-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIP5K1C	ENST00000589578.5	TSL:1	c.2022C>T	p.Pro674Pro	synonymous	Exon 17 of 17	ENSP00000466363.1	O60331-3
PIP5K1C	ENST00000537021.1	TSL:1	c.*312C>T		3_prime_UTR	Exon 17 of 17	ENSP00000444779.1	O60331-2
PIP5K1C	ENST00000335312.8	TSL:1 MANE Select	c.1920+1372C>T		intron	N/A	ENSP00000335333.3	O60331-1

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

258

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00638

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00274

AC:

367

AN:

133984

AF XY:

0.00226

show subpopulations

Gnomad AFR exome

AF:

0.000468

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00390

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000573

Gnomad OTH exome

AF:

0.000727

GnomAD4 exome

AF:

0.000710

AC:

982

AN:

1383380

Hom.:

Cov.:

AF XY:

0.000693

AC XY:

473

AN XY:

682626

show subpopulations

African (AFR)

AF:

0.000443

AC:

AN:

31590

American (AMR)

AF:

0.0123

AC:

438

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25164

East Asian (EAS)

AF:

0.00935

AC:

334

AN:

35726

South Asian (SAS)

AF:

0.000745

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.0000297

AC:

AN:

33654

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000658

AC:

AN:

1078756

Other (OTH)

AF:

0.00105

AC:

AN:

57888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

126

188

251

314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00168

AC:

256

AN:

152216

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.000529

AC:

AN:

41554

American (AMR)

AF:

0.0121

AC:

185

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00640

AC:

AN:

5160

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67996

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000513

Hom.:

Bravo

AF:

0.00235

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.017

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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