chr14-24261740-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP3BP4_ModerateBS1_SupportingBS2
The NM_000359.3(TGM1):c.463C>T(p.Arg155Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,614,122 control chromosomes in the GnomAD database, including 4 homozygotes. 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
NM_000359.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000509 AC: 128AN: 251424Hom.: 2 AF XY: 0.000442 AC XY: 60AN XY: 135896
GnomAD4 exome AF: 0.000252 AC: 369AN: 1461884Hom.: 4 Cov.: 32 AF XY: 0.000270 AC XY: 196AN XY: 727240
GnomAD4 genome AF: 0.000204 AC: 31AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74438
ClinVar
Submissions by phenotype
Autosomal recessive congenital ichthyosis 1 Uncertain:4
NM_000359.2(TGM1):c.463C>T(R155W) is a missense variant classified as a variant of uncertain significance in the context of TGM1-related autosomal recessive congenital ichthyosis. R155W has been observed in cases with relevant disease (PMID: 19262603, 25154629, 20021785). Functional assessments of this variant are not available in the literature. R155W has been observed in population frequency databases (gnomAD: EAS 0.65%). In summary, there is insufficient evidence to classify NM_000359.2(TGM1):c.463C>T(R155W) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. -
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
TGM1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at