20-50935242-T-TAAA
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1
The NM_003859.3(DPM1):c.679-7_679-6insTTT 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 0.0000422 in 1,420,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 0.000042 ( 0 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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 20-50935242-T-TAAA is Benign according to our data. Variant chr20-50935242-T-TAAA is described in ClinVar as [Benign]. Clinvar id is 464506.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000422 (60/1420506) while in subpopulation AFR AF= 0.00156 (48/30844). AF 95% confidence interval is 0.00121. There are 0 homozygotes in gnomad4_exome. There are 21 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.679-7_679-6insTTT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000371588.10 | |||
ADNP-AS1 | NR_110008.1 | n.149+3793_149+3794insAAA | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM1 | ENST00000371588.10 | c.679-7_679-6insTTT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003859.3 | P1 | |||
ADNP-AS1 | ENST00000558899.2 | n.149+3793_149+3794insAAA | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD3 genomes
Cov.:
29
GnomAD4 exome AF: 0.0000422 AC: 60AN: 1420506Hom.: 0 Cov.: 21 AF XY: 0.0000296 AC XY: 21AN XY: 709186
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60
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1420506
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21
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21
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709186
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GnomAD4 genome Cov.: 29
GnomAD4 genome
Cov.:
29
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital disorder of glycosylation type 1E Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2023 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at