rs138315817

Variant names:

• chr17-7585536-CCA-C
• rs138315817
• NM_004870.4:c.104-195_104-194delCA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004870.4(MPDU1):​c.104-195_104-194delCA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.47 (17236 hom., cov: 0)
• Consequence: MPDU1 NM_004870.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.675
• Publications: 2 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-7585536-CCA-C is Benign according to our data. Variant chr17-7585536-CCA-C is described in ClinVar as Benign. ClinVar VariationId is 1228784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	NM_004870.4	MANE Select	c.104-195_104-194delCA		intron	N/A	NP_004861.2	A0A0S2Z4W8
	MPDU1	NM_001330073.1		c.104-195_104-194delCA		intron	N/A	NP_001317002.1	J3QW43
	MPDU1	NR_024603.1		n.320-195_320-194delCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	ENST00000250124.11	TSL:1 MANE Select	c.104-195_104-194delCA		intron	N/A	ENSP00000250124.6	O75352-1
	MPDU1	ENST00000853390.1		c.104-195_104-194delCA		intron	N/A	ENSP00000523449.1
	MPDU1	ENST00000853388.1		c.104-195_104-194delCA		intron	N/A	ENSP00000523447.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 69306 AN: 147918 Hom.: 17243 Cov.: 0

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.490

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 69313 AN: 147998 Hom.: 17236 Cov.: 0 AF XY: 0.466 AC XY: 33519 AN XY: 71858

African (AFR) AF: 0.283 AC: 11425 AN: 40302

American (AMR) AF: 0.425 AC: 6362 AN: 14976

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2214 AN: 3436

East Asian (EAS) AF: 0.427 AC: 2156 AN: 5046

South Asian (SAS) AF: 0.634 AC: 2953 AN: 4660

European-Finnish (FIN) AF: 0.477 AC: 4563 AN: 9562

Middle Eastern (MID) AF: 0.624 AC: 181 AN: 290

European-Non Finnish (NFE) AF: 0.569 AC: 37981 AN: 66784

Other (OTH) AF: 0.489 AC: 1004 AN: 2054

Alfa AF: 0.434 Hom.: 807

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.68
Mutation Taster		=19/81	disease causing (long InDel)

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: rs138315817; hg19: chr17-7488854;