Genetic Variant MPDU1:c.507+44G>T (chr17-7587061-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_004870.4(MPDU1):c.507+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,451,758 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 0.000028 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

MPDU1
NM_004870.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.706

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000214 (28/1306510) while in subpopulation EAS AF = 0.000362 (14/38682). AF 95% confidence interval is 0.000218. There are 0 homozygotes in GnomAdExome4. There are 15 alleles in the male GnomAdExome4 subpopulation. Median coverage is 22. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDU1	NM_004870.4 link	c.507+44G>T		intron_variant	Intron 5 of 6	ENST00000250124.11	NP_004861.2	O75352-1A0A0S2Z4W8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDU1	ENST00000250124.11 link	c.507+44G>T		intron_variant	Intron 5 of 6	1	NM_004870.4	ENSP00000250124.6		O75352-1

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

145248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000692

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000208

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000246

AC:

AN:

243620

AF XY:

0.0000301

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1306510

Hom.:

Cov.:

AF XY:

0.0000229

AC XY:

AN XY:

656202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

29800

Gnomad4 AMR exome

AF:

0.0000227

AC:

AN:

44148

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25168

Gnomad4 EAS exome

AF:

0.000362

AC:

AN:

38682

Gnomad4 SAS exome

AF:

0.0000241

AC:

AN:

82914

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52554

Gnomad4 NFE exome

AF:

0.0000103

AC:

AN:

972578

Gnomad4 Remaining exome

AF:

0.0000181

AC:

AN:

55168

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

AF:

0.0000275

AC:

AN:

145248

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70342

show subpopulations

Gnomad4 AFR

AF:

0.0000255

AC:

0.0000255323

AN:

0.0000255323

Gnomad4 AMR

AF:

0.0000692

AC:

0.0000692233

AN:

0.0000692233

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000208

AC:

0.000208333

AN:

0.000208333

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000151

AC:

0.0000151098

AN:

0.0000151098

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.22

DANN

Benign

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over