chr14-93467670-G-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 12P and 2B. PVS1PP3_StrongBP6_Moderate
The NM_001395159.1(UNC79):c.23-1G>T variant causes a splice acceptor change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.067 ( 0 hom., cov: 0)
Exomes 𝑓: 0.21 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
UNC79
NM_001395159.1 splice_acceptor
NM_001395159.1 splice_acceptor
Scores
5
1
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
UNC79 (HGNC:19966): (unc-79 homolog, NALCN channel complex subunit) The NALCN channel is responsible for Na(+) leak currents. The protein encoded by this gene, along with UNC80, is an accessory subunit of the NALCN channel that contributes to the Ca(2+) sensitivity of the channel. [provided by RefSeq, Sep 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 6.4, offset of 11, new splice context is: tttatctatttgcttccaAGatc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 14-93467670-G-T is Benign according to our data. Variant chr14-93467670-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046578.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC79 | NM_001395159.1 | c.23-1G>T | splice_acceptor_variant | ENST00000695012.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC79 | ENST00000695012.1 | c.23-1G>T | splice_acceptor_variant | NM_001395159.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1420AN: 21348Hom.: 0 Cov.: 0 FAILED QC
GnomAD3 genomes
?
AF:
AC:
1420
AN:
21348
Hom.:
Cov.:
0
FAILED QC
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:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.210 AC: 33614AN: 160434Hom.: 0 Cov.: 0 AF XY: 0.196 AC XY: 15779AN XY: 80548
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
33614
AN:
160434
Hom.:
Cov.:
0
AF XY:
AC XY:
15779
AN XY:
80548
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 ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0666 AC: 1424AN: 21374Hom.: 0 Cov.: 0 AF XY: 0.0729 AC XY: 719AN XY: 9860
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1424
AN:
21374
Hom.:
Cov.:
0
AF XY:
AC XY:
719
AN XY:
9860
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ExAC
?
AF:
AC:
2390
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
UNC79-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 29, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 12
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at