rs75853379
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_199242.3(UNC13D):c.1744C>T(p.Leu582=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 1,606,538 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 134 hom., cov: 33)
Exomes 𝑓: 0.0049 ( 165 hom. )
Consequence
UNC13D
NM_199242.3 synonymous
NM_199242.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.41
Genes affected
UNC13D (HGNC:23147): (unc-13 homolog D) This gene encodes a protein that is a member of the UNC13 family, containing similar domain structure as other family members but lacking an N-terminal phorbol ester-binding C1 domain present in other Munc13 proteins. The protein appears to play a role in vesicle maturation during exocytosis and is involved in regulation of cytolytic granules secretion. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis type 3, a genetically heterogeneous, rare autosomal recessive disorder. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 17-75835513-G-A is Benign according to our data. Variant chr17-75835513-G-A is described in ClinVar as [Benign]. Clinvar id is 263218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=3.41 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.1744C>T | p.Leu582= | synonymous_variant | 20/32 | ENST00000207549.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.1744C>T | p.Leu582= | synonymous_variant | 20/32 | 1 | NM_199242.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0248 AC: 3773AN: 152184Hom.: 133 Cov.: 33
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GnomAD3 exomes AF: 0.0144 AC: 3339AN: 232320Hom.: 85 AF XY: 0.0122 AC XY: 1533AN XY: 126162
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GnomAD4 exome AF: 0.00491 AC: 7147AN: 1454236Hom.: 165 Cov.: 33 AF XY: 0.00482 AC XY: 3487AN XY: 722852
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GnomAD4 genome ? AF: 0.0249 AC: 3789AN: 152302Hom.: 134 Cov.: 33 AF XY: 0.0245 AC XY: 1823AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 12, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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