chr19-3632973-C-G

Position:

• chr19-3632973-C-G

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.*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

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=-0.96).
• BP6: Variant 19-3632973-C-G is Benign according to our data. Variant chr19-3632973-C-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP5K1C	NM_012398.3	c.*194G>C		3_prime_UTR_variant	18/18	ENST00000335312.8	NP_036530.1
PIP5K1C	NM_001195733.2	c.*194G>C		3_prime_UTR_variant	17/17		NP_001182662.1
PIP5K1C	XM_017026540.3	c.*194G>C		3_prime_UTR_variant	17/17		XP_016882029.1
PIP5K1C	XM_047438535.1	c.*194G>C		3_prime_UTR_variant	16/16		XP_047294491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8	c.*194G>C		3_prime_UTR_variant	18/18	1	NM_012398.3	ENSP00000335333	P3
PIP5K1C	ENST00000539785.5	c.*194G>C		3_prime_UTR_variant	17/17	2		ENSP00000445992	A1
PIP5K1C	ENST00000679885.1	c.*194G>C		3_prime_UTR_variant	19/19			ENSP00000504894	A1
PIP5K1C	ENST00000679828.1	c.*1740G>C		3_prime_UTR_variant, NMD_transcript_variant	19/19			ENSP00000506175

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

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0428

Gnomad4 NFE exome AF: 0.0695

Gnomad4 OTH exome AF: 0.131

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

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0427

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.193

Alfa AF: 0.0368 Hom.: 36

Bravo AF: 0.240

Asia WGS AF: 0.217 AC: 753 AN: 3476

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.52
DANN	Benign	0.65

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: rs28490078; hg19: chr19-3632971;