2-209772013-G-GCGGCGGCTAGCGAGGAGACAGAGCTGGGTCCTGCAGTAGGACTCCCGGGAGCCACCATTATGGTGAAGAGGAAGAGCTCCGAGGGCCAGGAGCAGGA
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001371986.1(UNC80):c.-52_45dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000883 in 1,132,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 8.8e-7 ( 0 hom. )
Consequence
UNC80
NM_001371986.1 5_prime_UTR
NM_001371986.1 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0290
Genes affected
UNC80 (HGNC:26582): (unc-80 homolog, NALCN channel complex subunit) The protein encoded by this gene is a component of a voltage-independent 'leak' ion-channel complex, in which it performs essential functions, such as serving as a bridge between two other components (sodium leak channel non-selective and UNC79) and as a scaffold for Src kinases. Leak channels play an importnat role in establishment and maintenance of resting membrane potentials in neurons. Mutations in this gene are associated with congenital infantile encephalopathy, intellectual disability and growth issues. [provided by RefSeq, Aug 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC80 | NM_001371986.1 | c.-52_45dup | 5_prime_UTR_variant | 1/65 | ENST00000673920.1 | ||
UNC80 | NM_032504.2 | c.-52_45dup | 5_prime_UTR_variant | 1/64 | |||
UNC80 | NM_182587.4 | c.-52_45dup | 5_prime_UTR_variant | 1/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC80 | ENST00000673920.1 | c.-52_45dup | 5_prime_UTR_variant | 1/65 | NM_001371986.1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 8.83e-7 AC: 1AN: 1132512Hom.: 0 Cov.: 15 AF XY: 0.00000175 AC XY: 1AN XY: 570548
GnomAD4 exome
AF:
AC:
1
AN:
1132512
Hom.:
Cov.:
15
AF XY:
AC XY:
1
AN XY:
570548
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the UNC80 gene. It does not change the encoded amino acid sequence of the UNC80 protein. This variant has not been reported in the literature in individuals affected with UNC80-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1352691). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.