chr20-50935242-T-TA

Variant names:

• chr20-50935242-T-TA
• rs11480415
• NM_003859.3:c.679-7_679-6insT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0770

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]

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

ACMG classification

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 [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 rank	MANE	Protein	UniProt
DPM1	NM_003859.3	c.679-7_679-6insT		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000371588.10	NP_003850.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.102 AC: 12651 AN: 124268 Hom.: 1369 Cov.: 29

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

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.: 21 AF XY: 0.0184 AC XY: 13012 AN XY: 707286

Gnomad4 AFR exome AF: 0.215 AC: 6501 AN: 30266

Gnomad4 AMR exome AF: 0.0238 AC: 1028 AN: 43224

Gnomad4 ASJ exome AF: 0.0381 AC: 968 AN: 25438

Gnomad4 EAS exome AF: 0.0170 AC: 669 AN: 39238

Gnomad4 SAS exome AF: 0.0226 AC: 1898 AN: 83828

Gnomad4 FIN exome AF: 0.0102 AC: 540 AN: 53160

Gnomad4 NFE exome AF: 0.0122 AC: 13112 AN: 1077508

Gnomad4 Remaining exome AF: 0.0324 AC: 1903 AN: 58684

GnomAD4 genome AF: 0.102 AC: 12678 AN: 124324 Hom.: 1377 Cov.: 29 AF XY: 0.0991 AC XY: 6013 AN XY: 60704

Gnomad4 AFR AF: 0.363 AC: 0.362847 AN: 0.362847

Gnomad4 AMR AF: 0.0471 AC: 0.04712 AN: 0.04712

Gnomad4 ASJ AF: 0.0501 AC: 0.0501285 AN: 0.0501285

Gnomad4 EAS AF: 0.0293 AC: 0.0292553 AN: 0.0292553

Gnomad4 SAS AF: 0.0355 AC: 0.0355342 AN: 0.0355342

Gnomad4 FIN AF: 0.0172 AC: 0.0171857 AN: 0.0171857

Gnomad4 NFE AF: 0.0182 AC: 0.0182421 AN: 0.0182421

Gnomad4 OTH AF: 0.0828 AC: 0.0827664 AN: 0.0827664

Alfa AF: 0.0143 Hom.: 2

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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
Mutation Taster		=100/0	polymorphism (auto)

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: rs11480415; hg19: chr20-49551779; COSMIC: COSV65373423; COSMIC: COSV65373423;