rs112501965
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_199242.3(UNC13D):c.1992+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,613,908 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 30 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 35 hom. )
Consequence
UNC13D
NM_199242.3 intron
NM_199242.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.810
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 17-75834909-A-G is Benign according to our data. Variant chr17-75834909-A-G is described in ClinVar as [Benign]. Clinvar id is 263221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75834909-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1775/152212) while in subpopulation AFR AF= 0.0413 (1716/41502). AF 95% confidence interval is 0.0397. There are 30 homozygotes in gnomad4. There are 811 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.1992+11T>C | intron_variant | ENST00000207549.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.1992+11T>C | intron_variant | 1 | NM_199242.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0116 AC: 1767AN: 152094Hom.: 30 Cov.: 32
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GnomAD3 exomes AF: 0.00307 AC: 772AN: 251332Hom.: 13 AF XY: 0.00226 AC XY: 307AN XY: 135872
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GnomAD4 exome AF: 0.00121 AC: 1763AN: 1461696Hom.: 35 Cov.: 33 AF XY: 0.00103 AC XY: 750AN XY: 727160
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GnomAD4 genome ? AF: 0.0117 AC: 1775AN: 152212Hom.: 30 Cov.: 32 AF XY: 0.0109 AC XY: 811AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:3
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 | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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