chr19-3633625-G-A

Position:

• chr19-3633625-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012398.3(PIP5K1C):​c.1921-105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 738,270 control chromosomes in the GnomAD database, including 2,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (344 hom., cov: 33)
  • Exomes 𝑓: 0.071 (1760 hom.)
• Consequence: PIP5K1C NM_012398.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.130

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 19-3633625-G-A is Benign according to our data. Variant chr19-3633625-G-A is described in ClinVar as [Benign]. Clinvar id is 1246764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP5K1C	NM_012398.3	c.1921-105C>T		intron_variant		ENST00000335312.8	NP_036530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8	c.1921-105C>T		intron_variant		1	NM_012398.3	ENSP00000335333	P3
PIP5K1C	ENST00000539785.5	c.1921-456C>T		intron_variant		2		ENSP00000445992	A1
PIP5K1C	ENST00000679885.1	c.1999-105C>T		intron_variant				ENSP00000504894	A1
PIP5K1C	ENST00000679828.1	c.*1460-105C>T		intron_variant, NMD_transcript_variant				ENSP00000506175

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8418 AN: 152088 Hom.: 344 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.0589

GnomAD4 exome AF: 0.0709 AC: 41565 AN: 586064 Hom.: 1760 AF XY: 0.0707 AC XY: 20544 AN XY: 290600

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0379

Gnomad4 ASJ exome AF: 0.0537

Gnomad4 EAS exome AF: 0.000115

Gnomad4 SAS exome AF: 0.0315

Gnomad4 FIN exome AF: 0.0738

Gnomad4 NFE exome AF: 0.0808

Gnomad4 OTH exome AF: 0.0569

GnomAD4 genome AF: 0.0553 AC: 8416 AN: 152206 Hom.: 344 Cov.: 33 AF XY: 0.0533 AC XY: 3964 AN XY: 74414

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0668 Hom.: 56

Bravo AF: 0.0518

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.92

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

LitVar

Other links and lift over

dbSNP: rs17606167; hg19: chr19-3633623;