17-7587480-GG-TC

Variant names:

• chr17-7587480-GG-TC
• NM_004870.4:c.673_674delGGinsTC
• MPDU1 p.Gly225Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004870.4(MPDU1):​c.673_674delGGinsTC​(p.Gly225Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MPDU1 NM_004870.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.76
• Publications: 0 publications found

Genes affected

MPDU1 (HGNC:7207): (mannose-P-dolichol utilization defect 1) This gene encodes an endoplasmic reticulum membrane protein that is required for utilization of the mannose donor mannose-P-dolichol in the synthesis of lipid-linked oligosaccharides and glycosylphosphatidylinositols. Mutations in this gene result in congenital disorder of glycosylation type If. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

MPDU1 Gene-Disease associations (from GenCC):

• MPDU1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004870.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	NM_004870.4	MANE Select	c.673_674delGGinsTC	p.Gly225Ser	missense	N/A	NP_004861.2	A0A0S2Z4W8
	MPDU1	NM_001330073.1		c.*36_*37delGGinsTC		3_prime_UTR	Exon 6 of 6	NP_001317002.1	J3QW43
	MPDU1	NR_024603.1		n.884_885delGGinsTC		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	ENST00000250124.11	TSL:1 MANE Select	c.673_674delGGinsTC	p.Gly225Ser	missense	N/A	ENSP00000250124.6	O75352-1
	MPDU1	ENST00000571877.1	TSL:1	n.858_859delGGinsTC		non_coding_transcript_exon	Exon 2 of 2
	MPDU1	ENST00000853390.1		c.664_665delGGinsTC	p.Gly222Ser	missense	N/A	ENSP00000523449.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-7490798;