17-7587859-G-A

Variant names:

• chr17-7587859-G-A
• rs4227
• NM_004870.4:c.*308G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004870.4(MPDU1):​c.*308G>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPDU1 NM_004870.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 66 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.*308G>A		3_prime_UTR	Exon 7 of 7	NP_004861.2	A0A0S2Z4W8
	MPDU1	NM_001330073.1		c.*415G>A		3_prime_UTR	Exon 6 of 6	NP_001317002.1	J3QW43
	MPDU1	NR_024603.1		n.1263G>A		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.*308G>A		3_prime_UTR	Exon 7 of 7	ENSP00000250124.6	O75352-1
	MPDU1	ENST00000853390.1		c.*308G>A		3_prime_UTR	Exon 7 of 7	ENSP00000523449.1
	MPDU1	ENST00000853388.1		c.*308G>A		3_prime_UTR	Exon 7 of 7	ENSP00000523447.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 2

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 173337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.92
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4227; hg19: chr17-7491177;