19-17606311-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001080421.3(UNC13A):c.4855G>A(p.Val1619Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,549,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_001080421.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UNC13A | NM_001080421.3 | c.4855G>A | p.Val1619Met | missense_variant | Exon 44 of 44 | ENST00000519716.7 | NP_001073890.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000479 AC: 73AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000436 AC: 63AN: 144656Hom.: 0 AF XY: 0.000447 AC XY: 35AN XY: 78294
GnomAD4 exome AF: 0.000651 AC: 909AN: 1397266Hom.: 1 Cov.: 31 AF XY: 0.000647 AC XY: 446AN XY: 689578
GnomAD4 genome AF: 0.000479 AC: 73AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74516
ClinVar
Submissions by phenotype
UNC13A-related disorder Uncertain:1
The UNC13A c.4855G>A variant is predicted to result in the amino acid substitution p.Val1619Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.099% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-17717120-C-T). A different variant affecting the same amino acid (p.Val1619Gly) was reported in the homozygous state in an individual with epileptic encephalopathy with intractable seizures and global developmental delay, however, no additional information was provided (Table S1 and S3, Al-Dewik et al. 2019. PubMed ID: 30919572). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at