17-75827430-T-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_199242.3(UNC13D):c.*535A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
UNC13D
NM_199242.3 3_prime_UTR
NM_199242.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.838
Publications
0 publications found
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]
UNC13D Gene-Disease associations (from GenCC):
- familial hemophagocytic lymphohistiocytosis 3Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- hereditary hemophagocytic lymphohistiocytosisInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_199242.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| UNC13D | TSL:1 MANE Select | c.*535A>G | 3_prime_UTR | Exon 32 of 32 | ENSP00000207549.3 | Q70J99-1 | |||
| UNC13D | TSL:2 | c.*40A>G | 3_prime_UTR | Exon 33 of 33 | ENSP00000388093.1 | Q70J99-3 | |||
| UNC13D | c.*535A>G | 3_prime_UTR | Exon 33 of 33 | ENSP00000538159.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1271972Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 614936
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1271972
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
614936
African (AFR)
AF:
AC:
0
AN:
28056
American (AMR)
AF:
AC:
0
AN:
19626
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18798
East Asian (EAS)
AF:
AC:
0
AN:
34386
South Asian (SAS)
AF:
AC:
0
AN:
61312
European-Finnish (FIN)
AF:
AC:
0
AN:
29636
Middle Eastern (MID)
AF:
AC:
0
AN:
4400
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1022856
Other (OTH)
AF:
AC:
0
AN:
52902
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Familial hemophagocytic lymphohistiocytosis 3 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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