Genetic Variant MPDU1:c.507+44G>A (chr17-7587061-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004870.4(MPDU1):c.507+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,306,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MPDU1
NM_004870.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.706

Publications

8 publications found

Variant links:

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

MPDU1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004870.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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=-0.85).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPDU1	NM_004870.4	MANE Select	c.507+44G>A	intron	N/A	NP_004861.2	A0A0S2Z4W8
MPDU1	NM_001330073.1		c.450-100G>A	intron	N/A	NP_001317002.1	J3QW43
MPDU1	NR_024603.1		n.718+44G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPDU1	ENST00000250124.11	TSL:1 MANE Select	c.507+44G>A	intron	N/A	ENSP00000250124.6	O75352-1
MPDU1	ENST00000571877.1	TSL:1	n.593G>A	non_coding_transcript_exon	Exon 1 of 2
MPDU1	ENST00000853390.1		c.498+53G>A	intron	N/A	ENSP00000523449.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145248

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1306504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29800

American (AMR)

AF:

0.00

AC:

AN:

44148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

38682

South Asian (SAS)

AF:

0.00

AC:

AN:

82912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

0.00000206

AC:

AN:

972574

Other (OTH)

AF:

0.00

AC:

AN:

55168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

145248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70342

African (AFR)

AF:

0.00

AC:

AN:

39166

American (AMR)

AF:

0.00

AC:

AN:

14446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

4800

South Asian (SAS)

AF:

0.00

AC:

AN:

4370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9740

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66182

Other (OTH)

AF:

0.00

AC:

AN:

1942

Alfa

AF:

0.00

Hom.:

2148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.23

(source)

DANN

Benign

0.18

PhyloP100

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over