rs11480415

Positions:

• chr20-50935242-T-TA
• chr20-50935242-T-TAA
• chr20-50935242-T-TAAA

Variant summary

Our verdict is Benign. Variant got -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, 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
• 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

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	c.679-7_679-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371588.10
ADNP-AS1	NR_110008.1	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	c.679-7_679-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003859.3	P1
ADNP-AS1	ENST00000558899.2	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.: 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

GnomAD3 exomes AF: 0.0298 AC: 7020 AN: 235258 Hom.: 93 AF XY: 0.0263 AC XY: 3375 AN XY: 128104

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

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.: 29 AF XY: 0.0991 AC XY: 6013 AN XY: 60704

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.: 2

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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;