chr19-3633194-A-G

Variant names:

• chr19-3633194-A-G
• rs542462
• NM_012398.3:c.2005-25T>C

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.2005-25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 760,796 control chromosomes in the GnomAD database, including 9,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1792 hom., cov: 33)
  • Exomes 𝑓: 0.15 (7752 hom.)
• Consequence: PIP5K1C NM_012398.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.248

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-3633194-A-G is Benign according to our data. Variant chr19-3633194-A-G is described in ClinVar as [Benign]. Clinvar id is 1243421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP5K1C	NM_012398.3	c.2005-25T>C		intron_variant	Intron 17 of 17	ENST00000335312.8	NP_036530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP5K1C	ENST00000335312.8	c.2005-25T>C		intron_variant	Intron 17 of 17	1	NM_012398.3	ENSP00000335333.3
PIP5K1C	ENST00000679885.1	c.2083-25T>C		intron_variant	Intron 18 of 18			ENSP00000504894.1
PIP5K1C	ENST00000539785.5	c.1921-25T>C		intron_variant	Intron 16 of 16	2		ENSP00000445992.1
PIP5K1C	ENST00000679828.1	n.*1544-25T>C		intron_variant	Intron 18 of 18			ENSP00000506175.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22631 AN: 151896 Hom.: 1792 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.149 AC: 31660 AN: 212526 AF XY: 0.146

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.326

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.152 AC: 92320 AN: 608782 Hom.: 7752 Cov.: 0 AF XY: 0.148 AC XY: 49113 AN XY: 330758

Gnomad4 AFR exome AF: 0.137 AC: 2376 AN: 17366

Gnomad4 AMR exome AF: 0.124 AC: 5067 AN: 40816

Gnomad4 ASJ exome AF: 0.202 AC: 4136 AN: 20466

Gnomad4 EAS exome AF: 0.326 AC: 11416 AN: 35038

Gnomad4 SAS exome AF: 0.113 AC: 7568 AN: 67066

Gnomad4 FIN exome AF: 0.141 AC: 7142 AN: 50590

Gnomad4 NFE exome AF: 0.144 AC: 48963 AN: 341084

Gnomad4 Remaining exome AF: 0.157 AC: 5054 AN: 32246

GnomAD4 genome AF: 0.149 AC: 22632 AN: 152014 Hom.: 1792 Cov.: 33 AF XY: 0.147 AC XY: 10928 AN XY: 74320

Gnomad4 AFR AF: 0.139 AC: 0.139344 AN: 0.139344

Gnomad4 AMR AF: 0.127 AC: 0.127239 AN: 0.127239

Gnomad4 ASJ AF: 0.199 AC: 0.199424 AN: 0.199424

Gnomad4 EAS AF: 0.326 AC: 0.325568 AN: 0.325568

Gnomad4 SAS AF: 0.120 AC: 0.119917 AN: 0.119917

Gnomad4 FIN AF: 0.136 AC: 0.135651 AN: 0.135651

Gnomad4 NFE AF: 0.147 AC: 0.146863 AN: 0.146863

Gnomad4 OTH AF: 0.146 AC: 0.145558 AN: 0.145558

Alfa AF: 0.137 Hom.: 784

Bravo AF: 0.153

Asia WGS AF: 0.194 AC: 672 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.64
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

Publications

LitVar

Other links and lift over

dbSNP: rs542462; hg19: chr19-3633192; COSMIC: COSV58949941; COSMIC: COSV58949941;