rs1423024691

Variant names:

• chr1-155139996-C-G
• rs1423024691
• NM_153741.2:c.245G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-155139996-C-G
• chr1-155139996-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_153741.2(DPM3):​c.245G>C​(p.Arg82Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPM3 NM_153741.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• DPM3-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.41583 (below the threshold of 3.09). Trascript score misZ: 0.49806 (below the threshold of 3.09). GenCC associations: The gene is linked to DPM3-congenital disorder of glycosylation.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153741.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPM3	NM_153741.2	MANE Select	c.245G>C	p.Arg82Pro	missense	Exon 2 of 2	NP_714963.1	Q9P2X0-1
	DPM3	NM_018973.4		c.335G>C	p.Arg112Pro	missense	Exon 1 of 1	NP_061846.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPM3	ENST00000368400.5	TSL:1 MANE Select	c.245G>C	p.Arg82Pro	missense	Exon 2 of 2	ENSP00000357385.5	Q9P2X0-1
	DPM3	ENST00000368399.1	TSL:6	c.335G>C	p.Arg112Pro	missense	Exon 1 of 1	ENSP00000357384.1	Q9P2X0-2
	DPM3	ENST00000341298.3	TSL:2	c.245G>C	p.Arg82Pro	missense	Exon 2 of 2	ENSP00000344338.3	Q9P2X0-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.066	T
PhyloP100		1.1
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.73
MutPred		0.66		Loss of MoRF binding (P = 0.0071)
MVP		0.93
MPC		1.2
ClinPred		0.92	D
GERP RS		3.8
PromoterAI		-0.030	Neutral
Varity_R		0.80
gMVP		0.97
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs1423024691; hg19: chr1-155112472;