rs104894171

Variant names:

• chr10-87508507-A-G
• rs104894171
• NM_004897.5:c.809A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_004897.5(MINPP1):​c.809A>G​(p.Gln270Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MINPP1 NM_004897.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.51
• Publications: 2 publications found

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)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-87508507-A-G is Pathogenic according to our data. Variant chr10-87508507-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 5022.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004897.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINPP1	NM_004897.5	MANE Select	c.809A>G	p.Gln270Arg	missense	Exon 2 of 5	NP_004888.2
	MINPP1	NM_001178117.2		c.809A>G	p.Gln270Arg	missense	Exon 2 of 3	NP_001171588.1
	MINPP1	NM_001178118.2		c.206A>G	p.Gln69Arg	missense	Exon 2 of 5	NP_001171589.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINPP1	ENST00000371996.9	TSL:1 MANE Select	c.809A>G	p.Gln270Arg	missense	Exon 2 of 5	ENSP00000361064.4
	MINPP1	ENST00000371994.8	TSL:1	c.809A>G	p.Gln270Arg	missense	Exon 2 of 3	ENSP00000361062.4
	MINPP1	ENST00000536010.1	TSL:1	c.206A>G	p.Gln69Arg	missense	Exon 2 of 5	ENSP00000437823.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.000133 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Thyroid cancer, nonmedullary, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.73	N
REVEL	Uncertain	0.35
Sift	Benign	0.29	T
Sift4G	Benign	0.51	T
Polyphen		0.087	B
Vest4		0.22
MutPred		0.70		Gain of methylation at Q270 (P = 0.0276)
MVP		0.78
MPC		0.44
ClinPred		0.50	D
GERP RS		6.0
Varity_R		0.13
gMVP		0.44
Mutation Taster		=17/83	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs104894171; hg19: chr10-89268264;