dbSNP rs2302661: MPDU1:c.507+44G>C (chr17-7587061-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004870.4(MPDU1):c.507+44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,451,628 control chromosomes in the GnomAD database, including 238,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17527 hom., cov: 20)

Exomes 𝑓: 0.57 ( 221126 hom. )

Consequence

MPDU1
NM_004870.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-7587061-G-C is Benign according to our data. Variant chr17-7587061-G-C is described in ClinVar as Benign. ClinVar VariationId is 259559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

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>C	intron	N/A	NP_004861.2	A0A0S2Z4W8
MPDU1	NM_001330073.1		c.450-100G>C	intron	N/A	NP_001317002.1	J3QW43
MPDU1	NR_024603.1		n.718+44G>C	intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

68099

AN:

145146

Hom.:

17528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.490

GnomAD2 exomes

AF:

0.524

AC:

127702

AN:

243620

AF XY:

0.542

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.572

AC:

746688

AN:

1306362

Hom.:

221126

Cov.:

AF XY:

0.575

AC XY:

377120

AN XY:

656134

show subpopulations

African (AFR)

AF:

0.281

AC:

8359

AN:

29798

American (AMR)

AF:

0.372

AC:

16417

AN:

44134

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

16575

AN:

25164

East Asian (EAS)

AF:

0.432

AC:

16698

AN:

38682

South Asian (SAS)

AF:

0.639

AC:

52964

AN:

82906

European-Finnish (FIN)

AF:

0.486

AC:

25550

AN:

52540

Middle Eastern (MID)

AF:

0.639

AC:

3511

AN:

5496

European-Non Finnish (NFE)

AF:

0.592

AC:

575347

AN:

972478

Other (OTH)

AF:

0.567

AC:

31267

AN:

55164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

13798

27596

41393

55191

68989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14756

29512

44268

59024

73780

<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

AF:

0.469

AC:

68122

AN:

145266

Hom.:

17527

Cov.:

AF XY:

0.467

AC XY:

32867

AN XY:

70414

show subpopulations

African (AFR)

AF:

0.277

AC:

10880

AN:

39252

American (AMR)

AF:

0.421

AC:

6081

AN:

14452

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

2214

AN:

3402

East Asian (EAS)

AF:

0.417

AC:

1996

AN:

4786

South Asian (SAS)

AF:

0.635

AC:

2770

AN:

4360

European-Finnish (FIN)

AF:

0.479

AC:

4666

AN:

9732

Middle Eastern (MID)

AF:

0.642

AC:

181

AN:

282

European-Non Finnish (NFE)

AF:

0.573

AC:

37890

AN:

66146

Other (OTH)

AF:

0.488

AC:

958

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

1445

2890

4335

5780

7225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.453

Hom.:

2148

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.20

(source)

DANN

Benign

0.33

PhyloP100

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over