rs201702634
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_199242.3(UNC13D):c.754-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000714 in 1,608,874 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 4 hom. )
Consequence
UNC13D
NM_199242.3 intron
NM_199242.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.774
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 17-75840378-C-T is Benign according to our data. Variant chr17-75840378-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 263245.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00348 (529/152220) while in subpopulation AFR AF= 0.0118 (492/41530). AF 95% confidence interval is 0.011. There are 3 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.754-49G>A | intron_variant | ENST00000207549.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.754-49G>A | intron_variant | 1 | NM_199242.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00347 AC: 528AN: 152102Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00103 AC: 253AN: 244492Hom.: 2 AF XY: 0.000677 AC XY: 90AN XY: 132874
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GnomAD4 exome AF: 0.000425 AC: 619AN: 1456654Hom.: 4 Cov.: 33 AF XY: 0.000350 AC XY: 254AN XY: 724712
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GnomAD4 genome ? AF: 0.00348 AC: 529AN: 152220Hom.: 3 Cov.: 32 AF XY: 0.00313 AC XY: 233AN XY: 74444
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at