Genetic Variant INPP4A:c.949+52_949+57dupACACAC (chr2-98544045-G-GCACACA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134225.2(INPP4A):c.949+52_949+57dupACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,441,472 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 0.000033 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000062 ( 0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134225.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INPP4A	NM_001134225.2	MANE Select	c.949+52_949+57dupACACAC	intron	N/A	NP_001127697.1	Q96PE3-3
INPP4A	NM_001351425.2	MANE Plus Clinical	c.949+52_949+57dupACACAC	intron	N/A	NP_001338354.1	A0ABB0MUY6
INPP4A	NM_001134224.2		c.949+52_949+57dupACACAC	intron	N/A	NP_001127696.1	Q96PE3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INPP4A	ENST00000409851.8	TSL:1 MANE Select	c.949+38_949+39insCACACA	intron	N/A	ENSP00000386777.4	Q96PE3-3
INPP4A	ENST00000715854.1	MANE Plus Clinical	c.949+38_949+39insCACACA	intron	N/A	ENSP00000520526.1	A0ABB0MUY6
INPP4A	ENST00000523221.2	TSL:1	c.949+38_949+39insCACACA	intron	N/A	ENSP00000427722.1	Q96PE3-1

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150412

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000737

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000620

AC:

AN:

1291060

Hom.:

Cov.:

AF XY:

0.00000471

AC XY:

AN XY:

636348

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

29574

American (AMR)

AF:

0.00

AC:

AN:

33538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23022

East Asian (EAS)

AF:

0.00

AC:

AN:

33562

South Asian (SAS)

AF:

0.00

AC:

AN:

73084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5154

European-Non Finnish (NFE)

AF:

0.00000502

AC:

AN:

995706

Other (OTH)

AF:

0.00

AC:

AN:

53592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000332

AC:

AN:

150412

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73382

show subpopulations

African (AFR)

AF:

0.0000737

AC:

AN:

40728

American (AMR)

AF:

0.00

AC:

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.000194

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67588

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

390

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over