rs773403940
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_003859.3(DPM1):āc.757T>Gā(p.Leu253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,601,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L253L) has been classified as Likely benign.
Frequency
Consequence
NM_003859.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.757T>G | p.Leu253Val | missense_variant | 9/9 | ENST00000371588.10 | |
ADNP-AS1 | NR_110008.1 | n.149+3709A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM1 | ENST00000371588.10 | c.757T>G | p.Leu253Val | missense_variant | 9/9 | 1 | NM_003859.3 | P1 | |
ADNP-AS1 | ENST00000558899.2 | n.149+3709A>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000108 AC: 27AN: 251008Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135686
GnomAD4 exome AF: 0.0000207 AC: 30AN: 1449236Hom.: 0 Cov.: 27 AF XY: 0.0000222 AC XY: 16AN XY: 721992
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74316
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 253 of the DPM1 protein (p.Leu253Val). This variant is present in population databases (rs773403940, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with DPM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 533132). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at