rs117089191

chr15-74897148-C-Gchr15-74897148-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002435.3(MPI):c.982C>G(p.Arg328Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R328W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPI NM_002435.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

Genes affected

MPI (HGNC:7216): (mannose phosphate isomerase) Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18775973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPI	NM_002435.3	c.982C>G	p.Arg328Gly	missense_variant	7/8	ENST00000352410.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPI	ENST00000352410.9	c.982C>G	p.Arg328Gly	missense_variant	7/8	1	NM_002435.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	23
Dann	Benign	0.96
DEOGEN2	Uncertain	0.72	D;.;D;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	1.3	L;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.36	T;T;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.091	B;.;.;B
Vest4		0.27
MutPred		0.56		Loss of solvent accessibility (P = 0.0159);.;.;.;
MVP		0.81
MPC		0.26
ClinPred		0.10	T
GERP RS		3.1
Varity_R		0.15
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.81		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.81		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs117089191; hg19: chr15-75189489;