1-155140194-GA-CT

Variant names:

• chr1-155140194-GA-CT
• NM_153741.2:c.46_47delTCinsAG
• DPM3 p.17

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_153741.2(DPM3):​c.46_47delTCinsAG​(p.17) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S16S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPM3 NM_153741.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• 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), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.

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.46_47delTCinsAG	p.17	synonymous	N/A	NP_714963.1	Q9P2X0-1
	DPM3	NM_018973.4		c.136_137delTCinsAG	p.47	synonymous	N/A	NP_061846.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPM3	ENST00000368400.5	TSL:1 MANE Select	c.46_47delTCinsAG	p.17	synonymous	N/A	ENSP00000357385.5	Q9P2X0-1
	DPM3	ENST00000368399.1	TSL:6	c.136_137delTCinsAG	p.47	synonymous	N/A	ENSP00000357384.1	Q9P2X0-2
	DPM3	ENST00000341298.3	TSL:2	c.46_47delTCinsAG	p.17	synonymous	N/A	ENSP00000344338.3	Q9P2X0-1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-155112670;