Genetic Variant INPP5F:p.Gln5Arg (chr10-119726276-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014937.4(INPP5F):c.14A>G(p.Gln5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000742 in 1,334,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

INPP5F
NM_014937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Publications

0 publications found

Variant links:

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]

INPP5F links:

ENSG00000304934 (HGNC:):

ENSG00000304934 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23745304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014937.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INPP5F	NM_014937.4	MANE Select	c.14A>G	p.Gln5Arg	missense	Exon 1 of 20	NP_055752.1	Q9Y2H2-1
INPP5F	NM_001441000.1		c.14A>G	p.Gln5Arg	missense	Exon 1 of 20	NP_001427929.1
INPP5F	NM_001441002.1		c.14A>G	p.Gln5Arg	missense	Exon 1 of 20	NP_001427931.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INPP5F	ENST00000650623.2	MANE Select	c.14A>G	p.Gln5Arg	missense	Exon 1 of 20	ENSP00000497527.1	Q9Y2H2-1
INPP5F	ENST00000369081.3	TSL:1	c.14A>G	p.Gln5Arg	missense	Exon 1 of 5	ENSP00000489864.1	Q9Y2H2-3
INPP5F	ENST00000964566.1		c.14A>G	p.Gln5Arg	missense	Exon 1 of 21	ENSP00000634625.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000742

AC:

AN:

1334314

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

661602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27046

American (AMR)

AF:

0.00

AC:

AN:

29162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22382

East Asian (EAS)

AF:

0.00

AC:

AN:

28086

South Asian (SAS)

AF:

0.00

AC:

AN:

73684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5290

European-Non Finnish (NFE)

AF:

0.0000933

AC:

AN:

1050040

Other (OTH)

AF:

0.0000185

AC:

AN:

53998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.0052

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.16

Eigen

Benign

0.076

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

PhyloP100

2.4

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.81

REVEL

Benign

0.058

Sift

Benign

0.33

Sift4G

Benign

0.43

Polyphen

0.98

Vest4

0.20

MutPred

0.30

Loss of methylation at K7 (P = 0.0599)

MVP

0.29

MPC

0.59

ClinPred

0.93

GERP RS

3.5

PromoterAI

0.016

Neutral

(source)

Varity_R

0.26

gMVP

0.57

Mutation Taster

=74/26

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over