rs769696421

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004870.4(MPDU1):​c.23C>A​(p.Pro8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MPDU1
NM_004870.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574
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]
ENSG00000233223 (HGNC:40379): (MPDU1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14733547).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPDU1NM_004870.4 linkc.23C>A p.Pro8Gln missense_variant Exon 1 of 7 ENST00000250124.11 NP_004861.2 O75352-1A0A0S2Z4W8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MPDU1ENST00000250124.11 linkc.23C>A p.Pro8Gln missense_variant Exon 1 of 7 1 NM_004870.4 ENSP00000250124.6 O75352-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251286
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461778
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
5.7
DANN
Benign
0.85
DEOGEN2
Benign
0.0046
.;T;.;.;.;T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.52
T;T;T;T;T;T;T
M_CAP
Benign
0.082
D
MetaRNN
Benign
0.15
T;T;T;T;T;T;T
MetaSVM
Benign
-0.48
T
MutationAssessor
Benign
1.5
.;L;.;.;L;.;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.5
.;N;N;.;D;.;.
REVEL
Benign
0.23
Sift
Benign
0.22
.;T;D;.;D;.;.
Sift4G
Benign
0.12
T;D;D;D;D;D;D
Polyphen
0.048
.;B;.;.;.;.;.
Vest4
0.19
MutPred
0.38
Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);.;
MVP
0.43
MPC
0.36
ClinPred
0.60
D
GERP RS
-8.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.028
gMVP
0.51

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.

Other links and lift over

dbSNP: rs769696421; hg19: chr17-7487203; API