2-98539581-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134225.2(INPP4A):​c.724C>A​(p.His242Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

INPP4A
NM_001134225.2 missense

Scores

4
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.73
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INPP4ANM_001134225.2 linkc.724C>A p.His242Asn missense_variant Exon 10 of 25 ENST00000409851.8 NP_001127697.1 Q96PE3-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INPP4AENST00000409851.8 linkc.724C>A p.His242Asn missense_variant Exon 10 of 25 1 NM_001134225.2 ENSP00000386777.4 Q96PE3-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460078
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726302
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 15, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.724C>A (p.H242N) alteration is located in exon 10 (coding exon 8) of the INPP4A gene. This alteration results from a C to A substitution at nucleotide position 724, causing the histidine (H) at amino acid position 242 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.099
.;.;T;.;T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D;.
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.70
D;D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;M;M;M;M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.3
N;N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.90
T;T;T;T;T
Sift4G
Benign
0.30
T;T;T;T;T
Polyphen
1.0
D;D;D;D;D
Vest4
0.75
MutPred
0.39
Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP
0.52
MPC
1.0
ClinPred
0.98
D
GERP RS
5.3
Varity_R
0.15
gMVP
0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-99156044; API