rs772047932

Variant names:

• chr17-7583872-G-A
• rs772047932
• NM_004870.4:c.10G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7583872-G-A
• chr17-7583872-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004870.4(MPDU1):​c.10G>A​(p.Glu4Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E4E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MPDU1 NM_004870.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63
• Publications: 0 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-AS1 (HGNC:40379): (MPDU1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41885367).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	NM_004870.4	MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 1 of 7	NP_004861.2
	MPDU1	NM_001330073.1		c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	NP_001317002.1
	MPDU1	NR_024603.1		n.226G>A		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDU1	ENST00000250124.11	TSL:1 MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 1 of 7	ENSP00000250124.6
	MPDU1	ENST00000579445.5	TSL:3	c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	ENSP00000464158.1
	MPDU1	ENST00000396501.8	TSL:2	c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	ENSP00000379758.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250768 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461704 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111992

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	MPDU1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.29
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0027	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.34
MutPred		0.17		Gain of ubiquitination at E4 (P = 0.0325)
MVP		0.86
MPC		0.40
ClinPred		0.96	D
GERP RS		5.3
PromoterAI		-0.093	Neutral
Varity_R		0.46
gMVP		0.79
Mutation Taster		=87/13	polymorphism

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: rs772047932; hg19: chr17-7487190;