17-7583943-C-A

Variant names:

• chr17-7583943-C-A
• NM_004870.4:c.81C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004870.4(MPDU1):​c.81C>A​(p.Phe27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MPDU1 NM_004870.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.279

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]

ENSG00000233223 (HGNC:40379): (MPDU1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDU1	NM_004870.4	c.81C>A	p.Phe27Leu	missense_variant	Exon 1 of 7	ENST00000250124.11	NP_004861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDU1	ENST00000250124.11	c.81C>A	p.Phe27Leu	missense_variant	Exon 1 of 7	1	NM_004870.4	ENSP00000250124.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.81C>A (p.F27L) alteration is located in exon 1 (coding exon 1) of the MPDU1 gene. This alteration results from a C to A substitution at nucleotide position 81, causing the phenylalanine (F) at amino acid position 27 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.053	.;T;.;.;.;T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.77	T;T;T;T;T;T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.6	.;L;.;.;L;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.2	.;D;D;.;D;.;.;.
REVEL	Uncertain	0.39
Sift	Benign	0.14	.;T;T;.;T;.;.;.
Sift4G	Pathogenic	0.0	D;T;D;D;D;T;D;D
Polyphen		0.34	.;B;.;.;.;.;.;.
Vest4		0.24
MutPred		0.52		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;
MVP		0.76
MPC		0.42
ClinPred		0.94	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7487261;