chr17-7583881-G-C

Variant names:

• chr17-7583881-G-C
• NM_004870.4:c.19G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004870.4(MPDU1):​c.19G>C​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000048 (0 hom.)
• Consequence: MPDU1 NM_004870.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21621653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDU1	NM_004870.4	c.19G>C	p.Gly7Arg	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.19G>C	p.Gly7Arg	missense_variant	Exon 1 of 7	1	NM_004870.4	ENSP00000250124.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727188

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0033	.;T;.;.;.;T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.80	T;T;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.8	.;L;.;.;L;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.92	.;N;N;.;N;.;.
REVEL	Uncertain	0.38
Sift	Benign	0.086	.;T;D;.;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		0.0020	.;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		0.75
MPC		0.43
ClinPred		0.79	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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7487199;