chr17-34989496-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_013975.4(LIG3):c.722C>T(p.Ser241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_013975.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000219 AC: 55AN: 251272Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135816
GnomAD4 exome AF: 0.000145 AC: 212AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108AN XY: 727224
GnomAD4 genome AF: 0.000191 AC: 29AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74400
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: LIG3 c.722C>T (p.Ser241Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 251272 control chromosomes. The observed variant frequency is approximately 65.7- fold the estimated maximal expected allele frequency for a pathogenic variant in LIG3 causing Long QT Syndrome phenotype (3.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.722C>T in individuals affected with Long QT Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at