chr19-17618930-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001080421.3(UNC13A):c.4305G>A(p.Glu1435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,614,030 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00039 ( 4 hom. )
Consequence
UNC13A
NM_001080421.3 synonymous
NM_001080421.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0750
Genes affected
UNC13A (HGNC:23150): (unc-13 homolog A) This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 19-17618930-C-T is Benign according to our data. Variant chr19-17618930-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 728245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.075 with no splicing effect.
BS2
?
High AC in GnomAd at 310 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13A | NM_001080421.3 | c.4305G>A | p.Glu1435= | synonymous_variant | 39/44 | ENST00000519716.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13A | ENST00000519716.7 | c.4305G>A | p.Glu1435= | synonymous_variant | 39/44 | 5 | NM_001080421.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00204 AC: 310AN: 152210Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000662 AC: 165AN: 249274Hom.: 1 AF XY: 0.000525 AC XY: 71AN XY: 135230
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GnomAD4 exome AF: 0.000393 AC: 575AN: 1461702Hom.: 4 Cov.: 33 AF XY: 0.000378 AC XY: 275AN XY: 727136
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GnomAD4 genome ? AF: 0.00202 AC: 308AN: 152328Hom.: 2 Cov.: 32 AF XY: 0.00201 AC XY: 150AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
UNC13A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2019 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at