rs7495739

chr15-74893329-A-Cchr15-74893329-A-Gchr15-74893329-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002435.3(MPI):c.670+9A>C variant causes a intron 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MPI NM_002435.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113351464).
• BP6: Variant 15-74893329-A-C is Benign according to our data. Variant chr15-74893329-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 754799.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPI	NM_002435.3	c.670+9A>C		intron_variant		ENST00000352410.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPI	ENST00000352410.9	c.670+9A>C		intron_variant		1	NM_002435.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MPI-congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	4.2
Dann	Benign	0.93
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P
PROVEAN	Benign	-1.5	N
Sift	Benign	0.36	T
Sift4G	Benign	0.47	T
Vest4		0.15
MVP		0.96
GERP RS		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7495739; hg19: chr15-75185670;