14-93099810-T-A

Variant names:

• chr14-93099810-T-A
• rs34269820
• NM_014216.6:c.95+15259A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014216.6(ITPK1):​c.95+15259A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,676 control chromosomes in the GnomAD database, including 2,204 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2204 hom., cov: 31)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 3 publications found

Genes affected

ITPK1 (HGNC:6177): (inositol-tetrakisphosphate 1-kinase) This gene encodes an enzyme that belongs to the inositol 1,3,4-trisphosphate 5/6-kinase family. This enzyme regulates the synthesis of inositol tetraphosphate, and downstream products, inositol pentakisphosphate and inositol hexakisphosphate. Inositol metabolism plays a role in the development of the neural tube. Disruptions in this gene are thought to be associated with neural tube defects. A pseudogene of this gene has been identified on chromosome X. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014216.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	NM_014216.6	MANE Select	c.95+15259A>T		intron	N/A	NP_055031.2
	ITPK1	NM_001142593.3		c.95+15259A>T		intron	N/A	NP_001136065.1
	ITPK1	NM_001142594.3		c.95+15259A>T		intron	N/A	NP_001136066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	ENST00000267615.11	TSL:1 MANE Select	c.95+15259A>T		intron	N/A	ENSP00000267615.5
	ITPK1	ENST00000556603.6	TSL:1	c.95+15259A>T		intron	N/A	ENSP00000451091.1
	ITPK1	ENST00000354313.7	TSL:1	c.95+15259A>T		intron	N/A	ENSP00000346272.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23687 AN: 151558 Hom.: 2202 Cov.: 31

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23688 AN: 151676 Hom.: 2204 Cov.: 31 AF XY: 0.159 AC XY: 11786 AN XY: 74112

African (AFR) AF: 0.0537 AC: 2218 AN: 41330

American (AMR) AF: 0.144 AC: 2199 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3460

East Asian (EAS) AF: 0.145 AC: 742 AN: 5102

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4806

European-Finnish (FIN) AF: 0.196 AC: 2057 AN: 10480

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13623 AN: 67922

Other (OTH) AF: 0.184 AC: 388 AN: 2104

Alfa AF: 0.106 Hom.: 169

Bravo AF: 0.143

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.59
PhyloP100		1.0
Mutation Taster		=98/2	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: rs34269820; hg19: chr14-93566155;