Variant chr1-155139987-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_153741.2(DPM3):c.254T>A(p.Leu85Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

DPM3
NM_153741.2 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 8.13

Variant links:

Genes affected

DPM3 (HGNC:3007): (dolichyl-phosphate mannosyltransferase subunit 3, regulatory) Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. The protein encoded by this gene is a subunit of dolichyl-phosphate mannosyltransferase and acts as a stabilizer subunit of the dolichyl-phosphate mannosyltransferase complex. [provided by RefSeq, Jul 2008]

DPM3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0896 CDS is truncated, and there are 2 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-155139987-A-T is Pathogenic according to our data. Variant chr1-155139987-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 694278.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-155139987-A-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DPM3	NM_153741.2 linkuse as main transcript	c.254T>A	p.Leu85Ter	stop_gained	2/2	ENST00000368400.5	NP_714963.1
DPM3	NM_018973.4 linkuse as main transcript	c.344T>A	p.Leu115Ter	stop_gained	1/1		NP_061846.2
DPM3	XM_017001498.2 linkuse as main transcript	c.254T>A	p.Leu85Ter	stop_gained	2/2		XP_016856987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPM3	ENST00000368400.5 linkuse as main transcript	c.254T>A	p.Leu85Ter	stop_gained	2/2	1	NM_153741.2	ENSP00000357385	P1	Q9P2X0-1
DPM3	ENST00000368399.1 linkuse as main transcript	c.344T>A	p.Leu115Ter	stop_gained	1/1			ENSP00000357384		Q9P2X0-2
DPM3	ENST00000341298.3 linkuse as main transcript	c.254T>A	p.Leu85Ter	stop_gained	2/2	2		ENSP00000344338	P1	Q9P2X0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 25, 2020

- -

DPM3-congenital disorder of glycosylation

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Neurology Department, Peking University First Hospital

Jun 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.51

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

D;D;D

Vest4

0.25

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over