dbSNP rs2133234788: INPP5A:p.Val12Met (chr10-132538130-G-A) – 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_005539.5(INPP5A):c.34G>A(p.Val12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,113,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V12L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

INPP5A
NM_005539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.638

Publications

0 publications found

Variant links:

Genes affected

INPP5A (HGNC:6076): (inositol polyphosphate-5-phosphatase A) The protein encoded by this gene is a membrane-associated type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. [provided by RefSeq, Jul 2008]

INPP5A 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=0.18010262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5A	NM_005539.5 link	c.34G>A	p.Val12Met	missense_variant	Exon 1 of 16	ENST00000368594.8	NP_005530.3	Q14642

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
INPP5A	ENST00000368594.8 link	c.34G>A	p.Val12Met	missense_variant	Exon 1 of 16	1	NM_005539.5	ENSP00000357583.3	Q14642
INPP5A	ENST00000368593.7 link	c.34G>A	p.Val12Met	missense_variant	Exon 1 of 13	1		ENSP00000357582.3	Q5T1B5
INPP5A	ENST00000423490.5 link	c.-9G>A		upstream_gene_variant		5		ENSP00000390936.1	Q5T1B3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000180

AC:

AN:

1113022

Hom.:

Cov.:

AF XY:

0.00000376

AC XY:

AN XY:

532520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23430

American (AMR)

AF:

0.00

AC:

AN:

12102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15994

East Asian (EAS)

AF:

0.0000376

AC:

AN:

26592

South Asian (SAS)

AF:

0.00

AC:

AN:

30780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3748

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

932246

Other (OTH)

AF:

0.00

AC:

AN:

44666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

PhyloP100

0.64

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.20

Sift

Benign

0.12

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.70

P;P

Vest4

0.27

MutPred

0.53

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.59

MPC

1.2

ClinPred

0.23

GERP RS

1.1

PromoterAI

-0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.090

gMVP

0.41

Mutation Taster

=79/21

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over