3-49422391-C-CGGG
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000481.4(AMT):c.57_59dupCCC(p.Pro20dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P20P) has been classified as Likely benign.
Frequency
Consequence
NM_000481.4 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AMT | NM_000481.4 | c.57_59dupCCC | p.Pro20dup | disruptive_inframe_insertion | Exon 1 of 9 | ENST00000273588.9 | NP_000472.2 | |
NICN1 | NM_032316.3 | c.*2439_*2441dupCCC | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000273598.8 | NP_115692.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMT | ENST00000273588.9 | c.57_59dupCCC | p.Pro20dup | disruptive_inframe_insertion | Exon 1 of 9 | 1 | NM_000481.4 | ENSP00000273588.3 | ||
NICN1 | ENST00000273598.8 | c.*2439_*2441dupCCC | 3_prime_UTR_variant | Exon 6 of 6 | 1 | NM_032316.3 | ENSP00000273598.4 | |||
ENSG00000283189 | ENST00000636166.1 | c.496-822_496-820dupCCC | intron_variant | Intron 4 of 10 | 5 | ENSP00000490106.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000159 AC: 4AN: 250880 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461620Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4AN XY: 727112 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74288 show subpopulations
ClinVar
Submissions by phenotype
Glycine encephalopathy Uncertain:1
This variant, c.57_59dup, results in the insertion of 1 amino acid(s) of the AMT protein (p.Pro20dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs770510324, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 556727). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
Glycine encephalopathy 1 Uncertain:1
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at