Variant rs74336587 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004870.4(MPDU1):c.302+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,612,516 control chromosomes in the GnomAD database, including 595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 44 hom., cov: 31)

Exomes 𝑓: 0.026 ( 551 hom. )

Consequence

MPDU1
NM_004870.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.162

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-7586099-C-T is Benign according to our data. Variant chr17-7586099-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0185 (2810/152262) while in subpopulation NFE AF= 0.0277 (1886/68010). AF 95% confidence interval is 0.0267. There are 44 homozygotes in gnomad4. There are 1339 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDU1	NM_004870.4 linkuse as main transcript	c.302+21C>T		intron_variant		ENST00000250124.11	NP_004861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDU1	ENST00000250124.11 linkuse as main transcript	c.302+21C>T		intron_variant		1	NM_004870.4	ENSP00000250124	P1	O75352-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2809

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00548

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0223

AC:

5587

AN:

250732

Hom.:

AF XY:

0.0228

AC XY:

3087

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00469

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0248

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0247

GnomAD4 exome

AF:

0.0257

AC:

37540

AN:

1460254

Hom.:

551

Cov.:

AF XY:

0.0259

AC XY:

18833

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.00428

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0263

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.0282

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0185

AC:

2810

AN:

152262

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1339

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00546

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0215

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 17, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.8

DANN

Benign

0.39

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over