rs119486096

chr10-87505037-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 5021.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MINPP1	NM_004897.5	c.122C>T	p.Ser41Leu	missense_variant	1/5	ENST00000371996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MINPP1	ENST00000371996.9	c.122C>T	p.Ser41Leu	missense_variant	1/5	1	NM_004897.5	P1
MINPP1	ENST00000371994.8	c.122C>T	p.Ser41Leu	missense_variant	1/3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460882 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 726780

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Thyroid cancer, nonmedullary, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.86	D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.3e-7	A;A
PrimateAI	Uncertain	0.61	T
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	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.16
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs119486096; hg19: chr10-89264794; COSMIC: COSV64355513; COSMIC: COSV64355513;