chr1-40819949-C-T
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_004700.4(KCNQ4):c.909C>T(p.Phe303Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004700.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant nonsyndromic hearing loss 2AInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
- nonsyndromic genetic hearing lossInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hearing loss disorderInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Benign. The variant received -11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ4 | ENST00000347132.10 | c.909C>T | p.Phe303Phe | synonymous_variant | Exon 6 of 14 | 1 | NM_004700.4 | ENSP00000262916.6 | ||
KCNQ4 | ENST00000509682.6 | c.909C>T | p.Phe303Phe | synonymous_variant | Exon 6 of 13 | 5 | ENSP00000423756.2 | |||
KCNQ4 | ENST00000443478.3 | c.594C>T | p.Phe198Phe | synonymous_variant | Exon 5 of 13 | 5 | ENSP00000406735.3 | |||
KCNQ4 | ENST00000506017.1 | n.228C>T | non_coding_transcript_exon_variant | Exon 3 of 11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152242Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000159 AC: 4AN: 251476 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727244 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74376 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:1
p.Phe303Phe in exon 06 of KCNQ4: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, and it is not locat ed within the splice consensus sequence. This variant has been identified in 3/1 0406 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs141327099). -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at