chr20-50935242-T-TA

Position:

chr20-50935242-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003859.3(DPM1):c.679-7_679-6insT variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.0770

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 made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
DPM1	NM_003859.3 linkuse as main transcript	c.679-7_679-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371588.10
ADNP-AS1	NR_110008.1 linkuse as main transcript	n.149+3793_149+3794insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPM1	ENST00000371588.10 linkuse as main transcript	c.679-7_679-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003859.3	P1
ADNP-AS1	ENST00000558899.2 linkuse as main transcript	n.149+3793_149+3794insA		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes

AF:

0.0298

AC:

7020

AN:

235258

Hom.:

AF XY:

0.0263

AC XY:

3375

AN XY:

128104

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 SAS exome

AF:

0.0222

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

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.0381

Gnomad4 EAS exome

AF:

0.0170

Gnomad4 SAS exome

AF:

0.0226

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0324

GnomAD4 genome

AF:

0.102

AC:

12678

AN:

124324

Hom.:

1377

Cov.:

AF XY:

0.0991

AC XY:

6013

AN XY:

60704

show subpopulations

Gnomad4 AFR

AF:

0.363

Gnomad4 AMR

AF:

0.0471

Gnomad4 ASJ

AF:

0.0501

Gnomad4 EAS

AF:

0.0293

Gnomad4 SAS

AF:

0.0355

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0828

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

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 30, 2016	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

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

- -

Congenital disorder of glycosylation

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital disorder of glycosylation type 1E

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over