chr1-34761323-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_153212.3(GJB4):c.69C>G(p.Ile23Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I23F) has been classified as Likely benign.
Frequency
Consequence
NM_153212.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJB4 | NM_153212.3 | c.69C>G | p.Ile23Met | missense_variant | 2/2 | ENST00000339480.3 | |
GJB4 | XM_011540679.3 | c.69C>G | p.Ile23Met | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJB4 | ENST00000339480.3 | c.69C>G | p.Ile23Met | missense_variant | 2/2 | 2 | NM_153212.3 | P1 | |
SMIM12 | ENST00000426886.1 | c.208-42914G>C | intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000203 AC: 51AN: 251394Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135870
GnomAD4 exome AF: 0.000122 AC: 178AN: 1461714Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 88AN XY: 727174
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74376
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.69C>G (p.I23M) alteration is located in exon 2 (coding exon 1) of the GJB4 gene. This alteration results from a C to G substitution at nucleotide position 69, causing the isoleucine (I) at amino acid position 23 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at