chr6-135433187-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_001134831.2(AHI1):c.2106G>A(p.Thr702Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001134831.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152060Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248768Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134946
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460684Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726698
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74266
ClinVar
Submissions by phenotype
Joubert syndrome Pathogenic:1
This sequence change affects codon 702 of the AHI1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the AHI1 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with clinical features of Joubert syndrome (PMID: 34205586; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 461743). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at