rs148674319
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003859.3(DPM1):āc.61A>Gā(p.Ser21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S21R) has been classified as Uncertain significance.
Frequency
Consequence
NM_003859.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.61A>G | p.Ser21Gly | missense_variant | 1/9 | ENST00000371588.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM1 | ENST00000371588.10 | c.61A>G | p.Ser21Gly | missense_variant | 1/9 | 1 | NM_003859.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152112Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251348Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727226
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152112Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 21 of the DPM1 protein (p.Ser21Gly). This variant is present in population databases (rs148674319, gnomAD 0.006%). 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: 579929). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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