Genetic Variant INPP4A:c.949+56_949+57dupAC (chr2-98544045-G-GCA) – 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+56_949+57dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,435,952 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0022 ( 1 hom. )

Consequence

INPP4A
NM_001134225.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

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+56_949+57dupAC		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+38_949+39insCA		intron_variant	Intron 11 of 24	1	NM_001134225.2	ENSP00000386777.4		Q96PE3-3

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

203

AN:

150406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00231

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.000420

Gnomad FIN

AF:

0.000194

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00339

GnomAD2 exomes

AF:

0.00237

AC:

256

AN:

107972

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.00236

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00102

Gnomad EAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.000654

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00221

AC:

2838

AN:

1285436

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1375

AN XY:

633628

show subpopulations

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

African (AFR)

AF:

0.00197

AC:

AN:

29426

American (AMR)

AF:

0.00233

AC:

AN:

33422

Ashkenazi Jewish (ASJ)

AF:

0.000523

AC:

AN:

22948

East Asian (EAS)

AF:

0.00143

AC:

AN:

33474

South Asian (SAS)

AF:

0.00278

AC:

202

AN:

72752

European-Finnish (FIN)

AF:

0.000389

AC:

AN:

43676

Middle Eastern (MID)

AF:

0.00311

AC:

AN:

5140

European-Non Finnish (NFE)

AF:

0.00227

AC:

2252

AN:

991226

Other (OTH)

AF:

0.00290

AC:

155

AN:

53372

⚠️ 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: 0.388

Heterozygous variant carriers

146

291

437

582

728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00136

AC:

205

AN:

150516

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

73498

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

40844

American (AMR)

AF:

0.00231

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.000584

AC:

AN:

5134

South Asian (SAS)

AF:

0.000421

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.000194

AC:

AN:

10316

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00146

AC:

AN:

67580

Other (OTH)

AF:

0.00336

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00251

Hom.:

390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-98544045-GCACACACA-GCACACACACA

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