chr10-119820901-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014937.4(INPP5F):c.1942G>T(p.Ala648Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000522 in 1,608,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
INPP5F
NM_014937.4 missense
NM_014937.4 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: 7.79
Genes affected
INPP5F (HGNC:17054): (inositol polyphosphate-5-phosphatase F) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase and contains a Sac domain. The activity of this protein is specific for phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INPP5F | NM_014937.4 | c.1942G>T | p.Ala648Ser | missense_variant | 16/20 | ENST00000650623.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INPP5F | ENST00000650623.2 | c.1942G>T | p.Ala648Ser | missense_variant | 16/20 | NM_014937.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152094Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251418Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135888
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GnomAD4 exome AF: 0.0000522 AC: 76AN: 1456754Hom.: 0 Cov.: 27 AF XY: 0.0000538 AC XY: 39AN XY: 725132
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74286
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2023 | The c.1942G>T (p.A648S) alteration is located in exon 16 (coding exon 16) of the INPP5F gene. This alteration results from a G to T substitution at nucleotide position 1942, causing the alanine (A) at amino acid position 648 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.;.;.;.;.;.;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;.;N;.;.;.
REVEL
Uncertain
Sift
Benign
T;.;.;.;.;.;.;T;.;.;.
Sift4G
Benign
T;.;.;.;.;.;.;D;.;D;.
Polyphen
D;.;D;.;.;.;.;.;.;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at