rs555710402

Variant summary

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

The NM_004870.4(MPDU1):​c.19G>A​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MPDU1
NM_004870.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08
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)

Genome browser will be placed here

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=0.1281116).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPDU1NM_004870.4 linkc.19G>A p.Gly7Arg 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.19G>A p.Gly7Arg missense_variant Exon 1 of 7 1 NM_004870.4 ENSP00000250124.6 O75352-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251212
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135822
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:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461744
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727188
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:
0.000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152368
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.11
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0033
.;T;.;.;.;T;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.80
T;T;T;T;T;T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Benign
1.8
.;L;.;.;L;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.92
.;N;N;.;N;.;.
REVEL
Uncertain
0.35
Sift
Benign
0.086
.;T;D;.;D;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
0.0040
.;B;.;.;.;.;.
Vest4
0.22
MutPred
0.22
Loss of ubiquitination at K10 (P = 0.0304);Loss of ubiquitination at K10 (P = 0.0304);Loss of ubiquitination at K10 (P = 0.0304);Loss of ubiquitination at K10 (P = 0.0304);Loss of ubiquitination at K10 (P = 0.0304);Loss of ubiquitination at K10 (P = 0.0304);.;
MVP
0.74
MPC
0.43
ClinPred
0.70
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.11
gMVP
0.73

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: rs555710402; hg19: chr17-7487199; COSMIC: COSV51468102; COSMIC: COSV51468102; API