rs17606167

Variant names:

• chr19-3633625-G-A
• rs17606167
• NM_012398.3:c.1921-105C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3633625-G-A
• chr19-3633625-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.1921-105C>T		intron	N/A	NP_036530.1	O60331-1
	PIP5K1C	NM_001195733.2		c.1921-456C>T		intron	N/A	NP_001182662.1	O60331-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP5K1C	ENST00000335312.8	TSL:1 MANE Select	c.1921-105C>T		intron	N/A	ENSP00000335333.3	O60331-1
	PIP5K1C	ENST00000876625.1		c.2038-105C>T		intron	N/A	ENSP00000546684.1
	PIP5K1C	ENST00000967141.1		c.2023-105C>T		intron	N/A	ENSP00000637200.1

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

African (AFR) AF: 0.0120 AC: 170 AN: 14122

American (AMR) AF: 0.0379 AC: 445 AN: 11728

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 639 AN: 11898

East Asian (EAS) AF: 0.000115 AC: 3 AN: 26002

South Asian (SAS) AF: 0.0315 AC: 614 AN: 19472

European-Finnish (FIN) AF: 0.0738 AC: 1731 AN: 23462

Middle Eastern (MID) AF: 0.0448 AC: 119 AN: 2654

European-Non Finnish (NFE) AF: 0.0808 AC: 36241 AN: 448568

Other (OTH) AF: 0.0569 AC: 1603 AN: 28158

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

African (AFR) AF: 0.0142 AC: 591 AN: 41532

American (AMR) AF: 0.0473 AC: 724 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 198 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0335 AC: 162 AN: 4832

European-Finnish (FIN) AF: 0.0704 AC: 747 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0855 AC: 5815 AN: 67978

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0481 Hom.: 61

Bravo AF: 0.0518

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17606167; hg19: chr19-3633623;