rs28490078

Variant names:

• chr19-3632973-C-G
• rs28490078
• NM_012398.3:c.*194G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-3632973-C-G
• chr19-3632973-C-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.*194G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 523,978 control chromosomes in the GnomAD database, including 10,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (7262 hom., cov: 33)
  • Exomes 𝑓: 0.10 (3480 hom.)
• Consequence: PIP5K1C NM_012398.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.500
• Publications: 4 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: 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 19-3632973-C-G is Benign according to our data. Variant chr19-3632973-C-G is described in ClinVar as Benign. ClinVar VariationId is 1250109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 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.*194G>C		3_prime_UTR	Exon 18 of 18	NP_036530.1	O60331-1
	PIP5K1C	NM_001195733.2		c.*194G>C		3_prime_UTR	Exon 17 of 17	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.*194G>C		3_prime_UTR	Exon 18 of 18	ENSP00000335333.3	O60331-1
	PIP5K1C	ENST00000876625.1		c.*194G>C		3_prime_UTR	Exon 19 of 19	ENSP00000546684.1
	PIP5K1C	ENST00000967141.1		c.*194G>C		3_prime_UTR	Exon 18 of 18	ENSP00000637200.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33450 AN: 151958 Hom.: 7218 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.00551

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.102 AC: 37849 AN: 371902 Hom.: 3480 Cov.: 0 AF XY: 0.102 AC XY: 19890 AN XY: 195374

African (AFR) AF: 0.550 AC: 4497 AN: 8172

American (AMR) AF: 0.0801 AC: 1129 AN: 14100

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 1237 AN: 11334

East Asian (EAS) AF: 0.238 AC: 6032 AN: 25314

South Asian (SAS) AF: 0.142 AC: 4688 AN: 33016

European-Finnish (FIN) AF: 0.0428 AC: 1208 AN: 28240

Middle Eastern (MID) AF: 0.183 AC: 305 AN: 1666

European-Non Finnish (NFE) AF: 0.0695 AC: 15833 AN: 227750

Other (OTH) AF: 0.131 AC: 2920 AN: 22310

GnomAD4 genome AF: 0.221 AC: 33544 AN: 152076 Hom.: 7262 Cov.: 33 AF XY: 0.215 AC XY: 16018 AN XY: 74360

African (AFR) AF: 0.564 AC: 23397 AN: 41456

American (AMR) AF: 0.123 AC: 1881 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5166

South Asian (SAS) AF: 0.163 AC: 786 AN: 4820

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10602

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.0715 AC: 4860 AN: 67956

Other (OTH) AF: 0.193 AC: 409 AN: 2114

Alfa AF: 0.0368 Hom.: 36

Bravo AF: 0.240

Asia WGS AF: 0.217 AC: 753 AN: 3476

ClinVar

ClinVar submissions

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	-0.96
CADD	Benign	0.52
DANN	Benign	0.65
PhyloP100		-0.50
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: rs28490078; hg19: chr19-3632971;