rs782577883
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM4_SupportingPP5_Very_Strong
The NM_012079.6(DGAT1):c.629_631delCCT(p.Ser210del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,612,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
DGAT1
NM_012079.6 disruptive_inframe_deletion
NM_012079.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.74
Genes affected
DGAT1 (HGNC:2843): (diacylglycerol O-acyltransferase 1) This gene encodes an multipass transmembrane protein that functions as a key metabolic enzyme. The encoded protein catalyzes the conversion of diacylglycerol and fatty acyl CoA to triacylglycerol. This enzyme can also transfer acyl CoA to retinol. Activity of this protein may be associated with obesity and other metabolic diseases. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_012079.6. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 8-144318305-TAGG-T is Pathogenic according to our data. Variant chr8-144318305-TAGG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 548013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Ensembl
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GnomAD3 genomes 0.0000921 AC: 14AN: 152014Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000521 AC: 13AN: 249596Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135436
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GnomAD4 exome AF: 0.000120 AC: 175AN: 1460526Hom.: 0 AF XY: 0.000122 AC XY: 89AN XY: 726578
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GnomAD4 genome 0.0000921 AC: 14AN: 152014Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74246
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:6Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital diarrhea 7 with exudative enteropathy Pathogenic:4Uncertain:1
| Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jun 08, 2024 | - - |
| Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 30, 2022 | - - |
| Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 07, 2021 | - - |
| Uncertain significance, flagged submission | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 15, 2017 | - - |
| Likely pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Jul 30, 2020 | - - |
not provided Pathogenic:2
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 25, 2024 | This variant, c.629_631del, results in the deletion of 1 amino acid(s) of the DGAT1 protein (p.Ser210del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs782577883, gnomAD 0.01%). This variant has been observed in individual(s) with protein-losing enteropathy (PMID: 29604290, 31778854, 33607125). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 548013). Studies have shown that this variant alters DGAT1 gene expression (PMID: 29604290). For these reasons, this variant has been classified as Pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 09, 2021 | Published functional studies demonstrate a damaging effect with reduced DGAT1 protein levels observed in cells transfected with DGAT1 gene with this variant (van Rijn et al., 2018); In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31778854, 33144682, 33607125, 29604290) - |
See cases Uncertain:1
| Uncertain significance, flagged submission | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Jun 24, 2020 | ACMG classification criteria: PM2, PM4, PP3 - |
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