X-71224268-AACCGTCTTC-AACCGTCTTCACCGTCTTC
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4PP3
The NM_000166.6(GJB1):c.572_580dupCCGTCTTCA(p.Thr191_Phe193dup) variant causes a disruptive inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000166.6 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB1 | NM_000166.6 | c.572_580dupCCGTCTTCA | p.Thr191_Phe193dup | disruptive_inframe_insertion | Exon 2 of 2 | ENST00000361726.7 | NP_000157.1 | |
GJB1 | NM_001097642.3 | c.572_580dupCCGTCTTCA | p.Thr191_Phe193dup | disruptive_inframe_insertion | Exon 2 of 2 | NP_001091111.1 | ||
GJB1 | XM_011530907.3 | c.572_580dupCCGTCTTCA | p.Thr191_Phe193dup | disruptive_inframe_insertion | Exon 2 of 2 | XP_011529209.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 21
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 21
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth Neuropathy X Uncertain:1
This variant, c.572_580dup, results in the insertion of 3 amino acid(s) of the GJB1 protein (p.Thr191_Phe193dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease, type X (CMTX) (PMID: 17052905). ClinVar contains an entry for this variant (Variation ID: 21087). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Charcot-Marie-Tooth disease X-linked dominant 1 Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at