chr14-60645011-CAT-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_005982.4(SIX1):c.*1270_*1271del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 152,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SIX1
NM_005982.4 3_prime_UTR
NM_005982.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.560
Genes affected
SIX1 (HGNC:10887): (SIX homeobox 1) The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in limb development. Defects in this gene are a cause of autosomal dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000322 (49/152278) while in subpopulation EAS AF= 0.0054 (28/5188). AF 95% confidence interval is 0.00384. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 49 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIX1 | NM_005982.4 | c.*1270_*1271del | 3_prime_UTR_variant | 2/2 | ENST00000645694.3 | ||
SIX1 | XM_017021602.3 | c.*1544_*1545del | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIX1 | ENST00000645694.3 | c.*1270_*1271del | 3_prime_UTR_variant | 2/2 | NM_005982.4 | P1 | |||
SIX1 | ENST00000554986.2 | c.*1270_*1271del | 3_prime_UTR_variant | 2/2 | 3 | ||||
SIX1 | ENST00000555955.3 | n.2762_2763del | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152160Hom.: 0 Cov.: 33
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?
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 4Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 2
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
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GnomAD4 genome ? AF: 0.000322 AC: 49AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74458
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?
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nonsyndromic Hearing Loss, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Branchiootorenal Spectrum Disorders Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at