chr3-49422505-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The ENST00000395338.7(AMT):c.-55C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 in 1,553,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000395338.7 5_prime_UTR
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NICN1 | ENST00000273598 | c.*2328C>T | 3_prime_UTR_variant | Exon 6 of 6 | 1 | NM_032316.3 | ENSP00000273598.4 | |||
ENSG00000283189 | ENST00000636166.1 | c.496-933C>T | intron_variant | Intron 4 of 10 | 5 | ENSP00000490106.1 | ||||
AMT | ENST00000273588.9 | c.-55C>T | upstream_gene_variant | 1 | NM_000481.4 | ENSP00000273588.3 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000147 AC: 3AN: 204104Hom.: 0 AF XY: 0.0000270 AC XY: 3AN XY: 111214
GnomAD4 exome AF: 0.00000428 AC: 6AN: 1401588Hom.: 0 Cov.: 24 AF XY: 0.00000573 AC XY: 4AN XY: 698042
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74366
ClinVar
Submissions by phenotype
Glycine encephalopathy Pathogenic:2Uncertain:1
This variant occurs in a non-coding region of the AMT gene. It does not change the encoded amino acid sequence of the AMT protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with glycine encephalopathy (PMID: 19299230, 27362913). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56225). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. -
NM_000481.3(AMT):c.-55C>T is a non coding variant classified as a variant of uncertain significance in the context of glycine encephalopathy, AMT-related. c.-55C>T has been observed in cases with relevant disease (PMID: 27362913, 19299230). Functional assessments of this variant are not available in the literature. c.-55C>T has been observed in population frequency databases (gnomAD: OTH 0.017%). In summary, there is insufficient evidence to classify NM_000481.3(AMT):c.-55C>T as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. -
- -
Neurodevelopmental delay Pathogenic:1
- -
Glycine encephalopathy 1 Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at