chrX-71223169-AAAGG-CAAGT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000675609.1(GJB1):​c.-165-18_-165-14delinsCAAGT variant causes a splice polypyrimidine tract, intron 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

Genomes: not found (cov: 22)

Consequence

GJB1
ENST00000675609.1 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
Variant links:
Genes affected
GJB1 (HGNC:4283): (gap junction protein beta 1) This gene encodes a member of the gap junction protein family. The gap junction proteins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and small molecules between cells. According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. Mutations in this gene cause X-linked Charcot-Marie-Tooth disease, an inherited peripheral neuropathy. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GJB1NM_001097642.3 linkuse as main transcriptc.-16-523_-16-519delinsCAAGT intron_variant
GJB1XM_011530907.3 linkuse as main transcriptc.-17+403_-17+407delinsCAAGT intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GJB1ENST00000374029.2 linkuse as main transcriptc.-16-523_-16-519delinsCAAGT intron_variant 5 P1
GJB1ENST00000447581.2 linkuse as main transcriptc.-17+403_-17+407delinsCAAGT intron_variant 5 P1
GJB1ENST00000645009.2 linkuse as main transcriptc.-16-523_-16-519delinsCAAGT intron_variant P1

Frequencies

GnomAD3 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMay 15, 2017The c.-183_-179delAAAGGinsCAAGT variant has not been published as a pathogenic variant, nor hasit been reported as a benign variant to our knowledge. No data are available from control populationsto assess the frequency of this variant. The c.-183_-179delAAAGGinsCAAGT variant may affect a 5'regulatory region; however, in the absence of RNA/functional studies, the actual effect of this sequencechange in this individual is unknown. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1131691690; hg19: chrX-70443019; API