chr14-60645516-TAA-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_005982.4(SIX1):c.*765_*766del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)
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: 2.09
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00116 (172/147706) while in subpopulation SAS AF= 0.00192 (9/4692). AF 95% confidence interval is 0.00152. There are 0 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. Median coverage is 0. 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 172 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIX1 | NM_005982.4 | c.*765_*766del | 3_prime_UTR_variant | 2/2 | ENST00000645694.3 | ||
SIX1 | XM_017021602.3 | c.*1039_*1040del | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIX1 | ENST00000645694.3 | c.*765_*766del | 3_prime_UTR_variant | 2/2 | NM_005982.4 | P1 | |||
SIX1 | ENST00000554986.2 | c.*765_*766del | 3_prime_UTR_variant | 2/2 | 3 | ||||
SIX1 | ENST00000553535.2 | n.1308_1309del | non_coding_transcript_exon_variant | 3/3 | 3 | ||||
SIX1 | ENST00000555955.3 | n.2257_2258del | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00116 AC: 172AN: 147658Hom.: 0 Cov.: 0
GnomAD3 genomes
?
AF:
AC:
172
AN:
147658
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00116 AC: 172AN: 147706Hom.: 0 Cov.: 0 AF XY: 0.00104 AC XY: 75AN XY: 71868
GnomAD4 genome
?
AF:
AC:
172
AN:
147706
Hom.:
Cov.:
0
AF XY:
AC XY:
75
AN XY:
71868
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
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
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at