chr1-155140047-T-G

Variant names:

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

Variant summary

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

The NM_153741.2(DPM3):​c.194A>C​(p.His65Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H65R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPM3 NM_153741.2 missense
• Clinical Significance: Not reported in ClinVar
• 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>C	p.His65Pro	missense_variant	Exon 2 of 2	ENST00000368400.5	NP_714963.1
DPM3	NM_018973.4	c.284A>C	p.His95Pro	missense_variant	Exon 1 of 1		NP_061846.2
DPM3	XM_017001498.2	c.194A>C	p.His65Pro	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>C	p.His65Pro	missense_variant	Exon 2 of 2	1	NM_153741.2	ENSP00000357385.5
DPM3	ENST00000368399.1	c.284A>C	p.His95Pro	missense_variant	Exon 1 of 1	6		ENSP00000357384.1
DPM3	ENST00000341298.3	c.194A>C	p.His65Pro	missense_variant	Exon 2 of 2	2		ENSP00000344338.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.69	.;D;D
Eigen	Benign	-0.17
Eigen_PC	Benign	0.062
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.49
MutPred		0.54		.;Loss of catalytic residue at H65 (P = 0.0533);Loss of catalytic residue at H65 (P = 0.0533);
MVP		0.82
MPC		0.48
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.64
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155112523;