rs1555306116
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000359.3(TGM1):āc.1163T>Cā(p.Leu388Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000359.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM1 | NM_000359.3 | c.1163T>C | p.Leu388Pro | missense_variant | 8/15 | ENST00000206765.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM1 | ENST00000206765.11 | c.1163T>C | p.Leu388Pro | missense_variant | 8/15 | 1 | NM_000359.3 | P1 | |
TGM1 | ENST00000559136.1 | c.236T>C | p.Leu79Pro | missense_variant | 4/7 | 5 | |||
TGM1 | ENST00000544573.5 | c.-28-282T>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461778Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 727164
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 388 of the TGM1 protein (p.Leu388Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital ichthyosis (PMID: 27025581). ClinVar contains an entry for this variant (Variation ID: 551121). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGM1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Autosomal recessive congenital ichthyosis 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 15, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at