rs564329348
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_199242.3(UNC13D):c.3263C>T(p.Pro1088Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,606,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P1088P) has been classified as Likely benign.
Frequency
Consequence
NM_199242.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13D | NM_199242.3 | c.3263C>T | p.Pro1088Leu | missense_variant | 32/32 | ENST00000207549.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13D | ENST00000207549.9 | c.3263C>T | p.Pro1088Leu | missense_variant | 32/32 | 1 | NM_199242.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000131 AC: 3AN: 229288Hom.: 0 AF XY: 0.0000159 AC XY: 2AN XY: 126026
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1453784Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9AN XY: 722810
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74500
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1088 of the UNC13D protein (p.Pro1088Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with UNC13D-related conditions. ClinVar contains an entry for this variant (Variation ID: 581521). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.3263C>T (p.P1088L) alteration is located in exon 32 (coding exon 32) of the UNC13D gene. This alteration results from a C to T substitution at nucleotide position 3263, causing the proline (P) at amino acid position 1088 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at