chr14-93538125-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001395159.1(UNC79):c.1259C>T(p.Ala420Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
UNC79
NM_001395159.1 missense
NM_001395159.1 missense
Scores
3
12
Clinical Significance
Conservation
PhyloP100: 5.79
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, UNC79
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19707549).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC79 | NM_001395159.1 | c.1259C>T | p.Ala420Val | missense_variant | 12/52 | ENST00000695012.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC79 | ENST00000695012.1 | c.1259C>T | p.Ala420Val | missense_variant | 12/52 | NM_001395159.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251150Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135754
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727208
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2024 | The c.728C>T (p.A243V) alteration is located in exon 12 (coding exon 9) of the UNC79 gene. This alteration results from a C to T substitution at nucleotide position 728, causing the alanine (A) at amino acid position 243 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;.
REVEL
Benign
Sift
Benign
T;T;T;T;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.47
.;.;.;P;.
Vest4
MutPred
0.29
.;Gain of catalytic residue at E421 (P = 0.0157);Gain of catalytic residue at E421 (P = 0.0157);Gain of catalytic residue at E421 (P = 0.0157);.;
MVP
MPC
ClinPred
T
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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