chr20-50935242-T-TA

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_679-6insT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,541,218 control chromosomes in the GnomAD database, including 1,645 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1377 hom., cov: 29)

Exomes 𝑓: 0.019 ( 268 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-TA is Benign according to our data. Variant chr20-50935242-T-TA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 338752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 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_679-6insT		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_679-6insT		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_003859.3	ENSP00000360644.5		O60762

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

12651

AN:

124268

Hom.:

1369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.0501

Gnomad EAS

AF:

0.0292

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0360

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0831

GnomAD2 exomes

AF:

0.0298

AC:

7020

AN:

235258

AF XY:

0.0263

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.0222

Gnomad ASJ exome

AF:

0.0394

Gnomad EAS exome

AF:

0.0251

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0219

GnomAD4 exome

AF:

0.0189

AC:

26737

AN:

1416894

Hom.:

268

Cov.:

AF XY:

0.0184

AC XY:

13012

AN XY:

707286

show subpopulations

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

African (AFR)

AF:

0.215

AC:

6501

AN:

30266

American (AMR)

AF:

0.0238

AC:

1028

AN:

43224

Ashkenazi Jewish (ASJ)

AF:

0.0381

AC:

968

AN:

25438

East Asian (EAS)

AF:

0.0170

AC:

669

AN:

39238

South Asian (SAS)

AF:

0.0226

AC:

1898

AN:

83828

European-Finnish (FIN)

AF:

0.0102

AC:

540

AN:

53160

Middle Eastern (MID)

AF:

0.0213

AC:

118

AN:

5548

European-Non Finnish (NFE)

AF:

0.0122

AC:

13112

AN:

1077508

Other (OTH)

AF:

0.0324

AC:

1903

AN:

58684

⚠️ 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: 0.388

Heterozygous variant carriers

1053

2106

3159

4212

5265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.102

AC:

12678

AN:

124324

Hom.:

1377

Cov.:

AF XY:

0.0991

AC XY:

6013

AN XY:

60704

show subpopulations

African (AFR)

AF:

0.363

AC:

10233

AN:

28202

American (AMR)

AF:

0.0471

AC:

607

AN:

12882

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

156

AN:

3112

East Asian (EAS)

AF:

0.0293

AC:

132

AN:

4512

South Asian (SAS)

AF:

0.0355

AC:

155

AN:

4362

European-Finnish (FIN)

AF:

0.0172

AC:

149

AN:

8670

Middle Eastern (MID)

AF:

0.0379

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0182

AC:

1090

AN:

59752

Other (OTH)

AF:

0.0828

AC:

146

AN:

1764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

474

947

1421

1894

2368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0143

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

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 30, 2016

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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