chr1-155140054-T-A

Position:

• chr1-155140054-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_153741.2(DPM3):​c.187A>T​(p.Thr63Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPM3 NM_153741.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a chain Dolichol-phosphate mannosyltransferase subunit 3 (size 91) in uniprot entity DPM3_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_153741.2
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPM3	NM_153741.2	c.187A>T	p.Thr63Ser	missense_variant	2/2	ENST00000368400.5	NP_714963.1
DPM3	NM_018973.4	c.277A>T	p.Thr93Ser	missense_variant	1/1		NP_061846.2
DPM3	XM_017001498.2	c.187A>T	p.Thr63Ser	missense_variant	2/2		XP_016856987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPM3	ENST00000368400.5	c.187A>T	p.Thr63Ser	missense_variant	2/2	1	NM_153741.2	ENSP00000357385	P1
DPM3	ENST00000368399.1	c.277A>T	p.Thr93Ser	missense_variant	1/1			ENSP00000357384
DPM3	ENST00000341298.3	c.187A>T	p.Thr63Ser	missense_variant	2/2	2		ENSP00000344338	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.187A>T (p.T63S) alteration is located in exon 2 (coding exon 1) of the DPM3 gene. This alteration results from a A to T substitution at nucleotide position 187, causing the threonine (T) at amino acid position 63 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.86	.;D;D
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.30	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.039	D;D;D
Polyphen		0.90	.;P;P
Vest4		0.40
MutPred		0.75		.;Gain of disorder (P = 0.0657);Gain of disorder (P = 0.0657);
MVP		0.89
MPC		0.80
ClinPred		0.95	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-155112530;