14-88563646-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024824.5(ZC3H14):c.37-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024824.5 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000893 AC: 136AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251466Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135918
GnomAD4 exome AF: 0.0000759 AC: 111AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727224
GnomAD4 genome AF: 0.000893 AC: 136AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.000886 AC XY: 66AN XY: 74516
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: ZC3H14 c.37-5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00019 in 251466 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ZC3H14 causing Intellectual Disability, Autosomal Recessive 56, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.37-5C>T in individuals affected with Intellectual Disability, Autosomal Recessive 56 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at