dbSNP rs119486096: MINPP1:p.Ser41Leu (chr10-87505037-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_004897.5(MINPP1):c.122C>T(p.Ser41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MINPP1
NM_004897.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.88

Publications

4 publications found

Variant links:

Genes affected

MINPP1 (HGNC:7102): (multiple inositol-polyphosphate phosphatase 1) This gene encodes multiple inositol polyphosphate phosphatase; an enzyme that removes 3-phosphate from inositol phosphate substrates. It is the only enzyme known to hydrolzye inositol pentakisphosphate and inositol hexakisphosphate. This enzyme also converts 2,3 bisphosphoglycerate (2,3-BPG) to 2-phosphoglycerate; an activity formerly thought to be exclusive to 2,3-BPG synthase/2-phosphatase (BPGM) in the Rapoport-Luebering shunt of the glycolytic pathway.[provided by RefSeq, Sep 2009]

MINPP1 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 16
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 7
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
thyroid cancer, nonmedullary, 2
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

MINPP1 links:

ENSG00000286445 (HGNC:):

ENSG00000286445 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 10-87505037-C-T is Pathogenic according to our data. Variant chr10-87505037-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 5021.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINPP1	NM_004897.5 link	c.122C>T	p.Ser41Leu	missense_variant	Exon 1 of 5	ENST00000371996.9	NP_004888.2	Q9UNW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MINPP1	ENST00000371996.9 link	c.122C>T	p.Ser41Leu	missense_variant	Exon 1 of 5	1	NM_004897.5	ENSP00000361064.4	Q9UNW1-1
MINPP1	ENST00000371994.8 link	c.122C>T	p.Ser41Leu	missense_variant	Exon 1 of 3	1		ENSP00000361062.4	Q9UNW1-2
ENSG00000286445	ENST00000662700.1 link	n.-200G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460882

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726780

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111872

Other (OTH)

AF:

0.00

AC:

AN:

60370

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

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:

0.000656

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Thyroid cancer, nonmedullary, 2

Pathogenic:1

Apr 01, 2001

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.86

D;D

M_CAP

Uncertain

0.093

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

1.9

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.21

Sift

Benign

0.056

T;D

Sift4G

Benign

0.077

T;D

Polyphen

0.77

P;P

Vest4

0.30

MutPred

0.33

Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);

MVP

0.74

MPC

0.57

ClinPred

0.63

GERP RS

3.3

PromoterAI

0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.63

Mutation Taster

=11/89

disease causing (ClinVar)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over