chr1-6235908-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012405.4(ICMT):c.4G>T(p.Ala2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,121,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2E) has been classified as Uncertain significance.
Frequency
Consequence
NM_012405.4 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 |
---|---|---|---|---|---|---|---|
ICMT | NM_012405.4 | c.4G>T | p.Ala2Ser | missense_variant | 1/5 | ENST00000343813.10 | |
ICMT | XM_047416592.1 | c.4G>T | p.Ala2Ser | missense_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ICMT | ENST00000343813.10 | c.4G>T | p.Ala2Ser | missense_variant | 1/5 | 1 | NM_012405.4 | P1 | |
ICMT | ENST00000489498.5 | c.4G>T | p.Ala2Ser | missense_variant, NMD_transcript_variant | 1/6 | 1 | |||
ICMT-DT | ENST00000650463.1 | n.372+845C>A | intron_variant, non_coding_transcript_variant | ||||||
ICMT | ENST00000474756.1 | c.4G>T | p.Ala2Ser | missense_variant, NMD_transcript_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000667 AC: 1AN: 149990Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 2AN: 971214Hom.: 0 Cov.: 31 AF XY: 0.00000438 AC XY: 2AN XY: 457100
GnomAD4 genome ? AF: 0.00000667 AC: 1AN: 149990Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 73148
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2022 | The c.4G>T (p.A2S) alteration is located in exon 1 (coding exon 1) of the ICMT gene. This alteration results from a G to T substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at