rs140945833
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 10P and 4B. PVS1PP5_ModerateBS2
The ENST00000347132.10(KCNQ4):āc.1668C>Gā(p.Tyr556Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ). Synonymous variant affecting the same amino acid position (i.e. Y556Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000347132.10 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ4 | NM_004700.4 | c.1668C>G | p.Tyr556Ter | stop_gained | 12/14 | ENST00000347132.10 | NP_004691.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.1668C>G | p.Tyr556Ter | stop_gained | 12/14 | 1 | NM_004700.4 | ENSP00000262916 | P2 | |
KCNQ4 | ENST00000509682.6 | c.1506C>G | p.Tyr502Ter | stop_gained | 11/13 | 5 | ENSP00000423756 | A1 | ||
KCNQ4 | ENST00000443478.3 | c.1251C>G | p.Tyr417Ter | stop_gained | 11/13 | 5 | ENSP00000406735 | |||
KCNQ4 | ENST00000506017.1 | n.987C>G | non_coding_transcript_exon_variant | 9/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251450Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461700Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727150
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 2A Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Juno Genomics, Hangzhou Juno Genomics, Inc | - | PVS1 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at