X-71223169-AAAGG-CAAGT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79

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]

ACMG classification

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
GJB1	NM_001097642.3	c.-16-523_-16-519delinsCAAGT		intron_variant
GJB1	XM_011530907.3	c.-17+403_-17+407delinsCAAGT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJB1	ENST00000374029.2	c.-16-523_-16-519delinsCAAGT		intron_variant		5		P1
GJB1	ENST00000447581.2	c.-17+403_-17+407delinsCAAGT		intron_variant		5		P1
GJB1	ENST00000645009.2	c.-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

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2017

The 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1131691690; hg19: chrX-70443019;