Genetic Variant INPP4A:c.949+54_949+57delACAC (chr2-98544045-GCACA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001134225.2(INPP4A):c.949+54_949+57delACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,427,044 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

INPP4A
NM_001134225.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.508

Publications

4 publications found

Variant links:

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

INPP4A Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

INPP4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4A	NM_001134225.2 link	c.949+54_949+57delACAC		intron_variant	Intron 11 of 24	ENST00000409851.8	NP_001127697.1	Q96PE3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8 link	c.949+39_949+42delCACA		intron_variant	Intron 11 of 24	1	NM_001134225.2	ENSP00000386777.4		Q96PE3-3

Frequencies

GnomAD3 genomes

AF:

0.0000598

AC:

AN:

150402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00216

AC:

233

AN:

107972

AF XY:

0.00223

show subpopulations

Gnomad AFR exome

AF:

0.000674

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00409

Gnomad EAS exome

AF:

0.00276

Gnomad FIN exome

AF:

0.00294

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.00220

GnomAD4 exome

AF:

0.00117

AC:

1489

AN:

1276532

Hom.:

AF XY:

0.00118

AC XY:

739

AN XY:

628870

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000854

AC:

AN:

29278

American (AMR)

AF:

0.00139

AC:

AN:

33090

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

22642

East Asian (EAS)

AF:

0.00124

AC:

AN:

33010

South Asian (SAS)

AF:

0.00175

AC:

126

AN:

72156

European-Finnish (FIN)

AF:

0.000830

AC:

AN:

43388

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5070

European-Non Finnish (NFE)

AF:

0.00112

AC:

1100

AN:

984952

Other (OTH)

AF:

0.00115

AC:

AN:

52946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.260

Heterozygous variant carriers

201

402

604

805

1006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000598

AC:

AN:

150512

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

73498

show subpopulations

African (AFR)

AF:

0.0000979

AC:

AN:

40844

American (AMR)

AF:

0.0000660

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.000195

AC:

AN:

5134

South Asian (SAS)

AF:

0.000210

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67574

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00456

Hom.:

390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism

(source)

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

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2-98544045-GCACACACA-GCACA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over