17-7587061-G-C

Variant names:

• chr17-7587061-G-C
• rs2302661
• ENST00000571877.1:n.593G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000571877.1(MPDU1):​n.593G>C variant causes a non coding transcript exon 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 ENST00000571877.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.706
• Publications: 8 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

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 id 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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.469 AC: 68099 AN: 145146 Hom.: 17528 Cov.: 20

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

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.: 22 AF XY: 0.575 AC XY: 377120 AN XY: 656134

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

GnomAD4 genome AF: 0.469 AC: 68122 AN: 145266 Hom.: 17527 Cov.: 20 AF XY: 0.467 AC XY: 32867 AN XY: 70414

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

Alfa AF: 0.453 Hom.: 2148

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
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)

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: rs2302661; hg19: chr17-7490379; COSMIC: COSV51468660; COSMIC: COSV51468660;