rs187089611
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS1
The NM_001371986.1(UNC80):c.3877G>C(p.Glu1293Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,542,392 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 2 hom. )
Consequence
UNC80
NM_001371986.1 missense
NM_001371986.1 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 9.60
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, UNC80
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12687731).
BP6
?
Variant 2-209877990-G-C is Benign according to our data. Variant chr2-209877990-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 225080.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000225 (313/1390120) while in subpopulation MID AF= 0.015 (85/5658). AF 95% confidence interval is 0.0124. There are 2 homozygotes in gnomad4_exome. There are 152 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC80 | NM_001371986.1 | c.3877G>C | p.Glu1293Gln | missense_variant | 24/65 | ENST00000673920.1 | |
UNC80 | NM_032504.2 | c.3883G>C | p.Glu1295Gln | missense_variant | 24/64 | ||
UNC80 | NM_182587.4 | c.3868G>C | p.Glu1290Gln | missense_variant | 24/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC80 | ENST00000673920.1 | c.3877G>C | p.Glu1293Gln | missense_variant | 24/65 | NM_001371986.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152154Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000175 AC: 26AN: 148820Hom.: 0 AF XY: 0.000191 AC XY: 15AN XY: 78584
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GnomAD4 exome AF: 0.000225 AC: 313AN: 1390120Hom.: 2 Cov.: 30 AF XY: 0.000222 AC XY: 152AN XY: 685420
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74474
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2014 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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