NM_000214.3:c.3467T>C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_000214.3(JAG1):āc.3467T>Cā(p.Val1156Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000141 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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 Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251478Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135916
GnomAD4 exome AF: 0.000142 AC: 208AN: 1461894Hom.: 0 Cov.: 34 AF XY: 0.000140 AC XY: 102AN XY: 727248
GnomAD4 genome AF: 0.000131 AC: 20AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
The V1156A variant in the JAG1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V1156A variant is observed in 1/6614 (0.015%) alleles from individuals of Finnish background in the ExAC dataset (Lek et al., 2016). The V1156A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V1156A as a variant of uncertain significance. -
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JAG1: BS2 -
Tetralogy of Fallot;C1866053:Deafness, congenital heart defects, and posterior embryotoxon;C1956125:Alagille syndrome due to a JAG1 point mutation 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