rs1664697714

Variant names:

• chr1-155140047-T-C
• rs1664697714
• NM_153741.2:c.194A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-155140047-T-C
• chr1-155140047-T-G

Variant summary

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

The NM_153741.2(DPM3):​c.194A>G​(p.His65Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H65Y) has been classified 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: 7.00

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 8 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 rank	MANE	Protein	UniProt
DPM3	NM_153741.2	c.194A>G	p.His65Arg	missense_variant	Exon 2 of 2	ENST00000368400.5	NP_714963.1
DPM3	NM_018973.4	c.284A>G	p.His95Arg	missense_variant	Exon 1 of 1		NP_061846.2
DPM3	XM_017001498.2	c.194A>G	p.His65Arg	missense_variant	Exon 2 of 2		XP_016856987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPM3	ENST00000368400.5	c.194A>G	p.His65Arg	missense_variant	Exon 2 of 2	1	NM_153741.2	ENSP00000357385.5
DPM3	ENST00000368399.1	c.284A>G	p.His95Arg	missense_variant	Exon 1 of 1	6		ENSP00000357384.1
DPM3	ENST00000341298.3	c.194A>G	p.His65Arg	missense_variant	Exon 2 of 2	2		ENSP00000344338.3

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

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.194A>G (p.H65R) alteration is located in exon 2 (coding exon 1) of the DPM3 gene. This alteration results from a A to G substitution at nucleotide position 194, causing the histidine (H) at amino acid position 65 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	.;D;D
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.69	T
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.015	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.30	.;B;B
Vest4		0.37
MutPred		0.58		.;Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);
MVP		0.85
MPC		0.77
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.70

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

Other links and lift over

dbSNP: rs1664697714; hg19: chr1-155112523;