1-236795711-CCG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000254.3(MTR):c.12_13delGC(p.Leu5ProfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000254.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251188Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135882
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461798Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727208
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Methylcobalamin deficiency type cblG Pathogenic:1
This sequence change creates a premature translational stop signal (p.Leu5Profs*16) in the MTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTR are known to be pathogenic (PMID: 9683607, 12068375). This variant is present in population databases (rs752220849, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with methylcobalamin deficiency (PMID: 12068375). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at