10-87505072-T-G

Position:

• chr10-87505072-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1_Moderate PM2 PP3_Moderate PP5_Moderate

The NM_004897.5(MINPP1):​c.157T>G​(p.Tyr53Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MINPP1 NM_004897.5 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.51

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 Likely_pathogenic. Variant got 8 ACMG points.

• PS1: Transcript NM_004897.5 (MINPP1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914
• PP5: Variant 10-87505072-T-G is Pathogenic according to our data. Variant chr10-87505072-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1285619.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINPP1	NM_004897.5	c.157T>G	p.Tyr53Asp	missense_variant	1/5	ENST00000371996.9	NP_004888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINPP1	ENST00000371996.9	c.157T>G	p.Tyr53Asp	missense_variant	1/5	1	NM_004897.5	ENSP00000361064	P1
MINPP1	ENST00000371994.8	c.157T>G	p.Tyr53Asp	missense_variant	1/3	1		ENSP00000361062

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Pontocerebellar hypoplasia, type 16 Pathogenic:2

Likely pathogenic, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	Mar 28, 2022	This variant is interpreted as likely pathogenic for Pontocerebellar hypoplasia, type 16, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Well-established functional studies show a deleterious effect (PS3). -
Pathogenic, no assertion criteria provided	literature only	OMIM	Sep 08, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.3	D;D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.85
MutPred		0.71		Gain of disorder (P = 0.0093);Gain of disorder (P = 0.0093);
MVP		0.91
MPC		1.6
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.95
gMVP		0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-89264829;