rs782577883
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
Consequence
NM_012079.6 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152014Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000521 AC: 13AN: 249596Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135436
GnomAD4 exome AF: 0.000120 AC: 175AN: 1460526Hom.: 0 AF XY: 0.000122 AC XY: 89AN XY: 726578
GnomAD4 genome AF: 0.0000921 AC: 14AN: 152014Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74246
ClinVar
Submissions by phenotype
Congenital diarrhea 7 with exudative enteropathy Pathogenic:4Uncertain:1
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not provided Pathogenic:2
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. -
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
ACMG classification criteria: PM2, PM4, PP3 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at