rs11480415
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
NM_003859.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
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]
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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 | 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: 12651AN: 124268Hom.: 1369 Cov.: 29
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GnomAD3 exomes AF: 0.0298 AC: 7020AN: 235258Hom.: 93 AF XY: 0.0263 AC XY: 3375AN XY: 128104
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GnomAD4 exome AF: 0.0189 AC: 26737AN: 1416894Hom.: 268 Cov.: 21 AF XY: 0.0184 AC XY: 13012AN XY: 707286
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GnomAD4 genome ? AF: 0.102 AC: 12678AN: 124324Hom.: 1377 Cov.: 29 AF XY: 0.0991 AC XY: 6013AN XY: 60704
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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 | Invitae | Jan 31, 2024 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at