20-50935242-T-TAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003859.3(DPM1):c.679-7_679-6insTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,543,996 control chromosomes in the GnomAD database, including 95 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 82 hom., cov: 29)

Exomes 𝑓: 0.0018 ( 13 hom. )

Consequence

DPM1
NM_003859.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0770

Publications

3 publications found

Variant links:

Genes affected

DPM1 (HGNC:3005): (dolichyl-phosphate mannosyltransferase subunit 1, catalytic) 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. Human DPM1 lacks a carboxy-terminal transmembrane domain and signal sequence and is regulated by DPM2. Mutations in this gene are associated with congenital disorder of glycosylation type Ie. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

DPM1 links:

ADNP-AS1 (HGNC:51227): (ADNP antisense RNA 1)

ADNP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 20-50935242-T-TAA is Benign according to our data. Variant chr20-50935242-T-TAA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPM1	NM_003859.3 link	c.679-7_679-6insTT		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000371588.10	NP_003850.1	O60762A0A0S2Z4Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPM1	ENST00000371588.10 link	c.679-7_679-6insTT		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_003859.3	ENSP00000360644.5		O60762

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

2676

AN:

124312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0900

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000229

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0144

Gnomad NFE

AF:

0.000301

Gnomad OTH

AF:

0.0138

GnomAD2 exomes

AF:

0.00355

AC:

835

AN:

235258

AF XY:

0.00249

show subpopulations

Gnomad AFR exome

AF:

0.0549

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.000745

Gnomad EAS exome

AF:

0.000288

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00177

AC:

2515

AN:

1419624

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1071

AN XY:

708782

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0609

AC:

1851

AN:

30394

American (AMR)

AF:

0.00272

AC:

118

AN:

43400

Ashkenazi Jewish (ASJ)

AF:

0.000429

AC:

AN:

25654

East Asian (EAS)

AF:

0.000229

AC:

AN:

39316

South Asian (SAS)

AF:

0.000320

AC:

AN:

84300

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00288

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.000262

AC:

283

AN:

1078866

Other (OTH)

AF:

0.00337

AC:

198

AN:

58804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.371

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0216

AC:

2684

AN:

124372

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1264

AN XY:

60738

show subpopulations

African (AFR)

AF:

0.0901

AC:

2544

AN:

28238

American (AMR)

AF:

0.00722

AC:

AN:

12884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3112

East Asian (EAS)

AF:

0.00

AC:

AN:

4514

South Asian (SAS)

AF:

0.000229

AC:

AN:

4362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8676

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000301

AC:

AN:

59756

Other (OTH)

AF:

0.0136

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000830

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 20, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 12, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital disorder of glycosylation type 1E

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

DPM1-related disorder

Benign:1

Jul 01, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over