19-17618942-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001080421.3(UNC13A):c.4293T>C(p.Asn1431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
UNC13A
NM_001080421.3 synonymous
NM_001080421.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0170
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 19-17618942-A-G is Benign according to our data. Variant chr19-17618942-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3032415.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.017 with no splicing effect.
BS2
?
High AC in GnomAdExome at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13A | NM_001080421.3 | c.4293T>C | p.Asn1431= | synonymous_variant | 39/44 | ENST00000519716.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13A | ENST00000519716.7 | c.4293T>C | p.Asn1431= | synonymous_variant | 39/44 | 5 | NM_001080421.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249272Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135228
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GnomAD4 exome AF: 0.000109 AC: 160AN: 1461680Hom.: 0 Cov.: 33 AF XY: 0.000113 AC XY: 82AN XY: 727120
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
UNC13A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 14, 2023 | 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
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BayesDel_noAF
Benign
Cadd
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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