rs144999773
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP2BS2
The NM_000214.3(JAG1):c.521C>T(p.Thr174Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000214.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251398Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461852Hom.: 0 Cov.: 34 AF XY: 0.0000440 AC XY: 32AN XY: 727230
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74376
ClinVar
Submissions by phenotype
not provided Uncertain:2
The T174M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T174M variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The T174M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
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Tetralogy of Fallot;C1866053:Deafness, congenital heart defects, and posterior embryotoxon;C1956125:Alagille syndrome due to a JAG1 point mutation;C5562003:Charcot-Marie-Tooth disease, axonal, Type 2HH Uncertain:1
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Alagille syndrome due to a JAG1 point mutation Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at