10-87519366-T-G

Variant names:

• chr10-87519366-T-G
• rs7896327
• NM_004897.5:c.934-1670T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004897.5(MINPP1):​c.934-1670T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,060 control chromosomes in the GnomAD database, including 21,431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21431 hom., cov: 32)
• Consequence: MINPP1 NM_004897.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINPP1	NM_004897.5	c.934-1670T>G		intron_variant	Intron 3 of 4	ENST00000371996.9	NP_004888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINPP1	ENST00000371996.9	c.934-1670T>G		intron_variant	Intron 3 of 4	1	NM_004897.5	ENSP00000361064.4
MINPP1	ENST00000371994.8	c.835+10833T>G		intron_variant	Intron 2 of 2	1		ENSP00000361062.4
MINPP1	ENST00000536010.1	c.331-1670T>G		intron_variant	Intron 3 of 4	1		ENSP00000437823.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78173 AN: 151942 Hom.: 21434 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78204 AN: 152060 Hom.: 21431 Cov.: 32 AF XY: 0.507 AC XY: 37653 AN XY: 74326

African (AFR) AF: 0.339 AC: 14081 AN: 41480

American (AMR) AF: 0.469 AC: 7175 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2122 AN: 3472

East Asian (EAS) AF: 0.356 AC: 1842 AN: 5170

South Asian (SAS) AF: 0.588 AC: 2825 AN: 4808

European-Finnish (FIN) AF: 0.505 AC: 5335 AN: 10558

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42933 AN: 67976

Other (OTH) AF: 0.526 AC: 1108 AN: 2106

Alfa AF: 0.487 Hom.: 3297

Bravo AF: 0.503

Asia WGS AF: 0.485 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs7896327; hg19: chr10-89279123;