chr19-17606221-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001080421.3(UNC13A):c.4945G>C(p.Ala1649Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,399,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
UNC13A
NM_001080421.3 missense
NM_001080421.3 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 3.76
Genes affected
UNC13A (HGNC:23150): (unc-13 homolog A) This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, UNC13A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3598528).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13A | NM_001080421.3 | c.4945G>C | p.Ala1649Pro | missense_variant | 44/44 | ENST00000519716.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13A | ENST00000519716.7 | c.4945G>C | p.Ala1649Pro | missense_variant | 44/44 | 5 | NM_001080421.3 | A2 | |
UNC13A | ENST00000551649.5 | c.5002G>C | p.Ala1668Pro | missense_variant | 45/45 | 5 | P3 | ||
UNC13A | ENST00000552293.5 | c.4927G>C | p.Ala1643Pro | missense_variant | 42/42 | 5 | A2 | ||
UNC13A | ENST00000550896.1 | c.4864G>C | p.Ala1622Pro | missense_variant | 40/40 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1399772Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1AN XY: 691054
GnomAD4 exome
AF:
AC:
1
AN:
1399772
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
691054
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2023 | The c.4945G>C (p.A1649P) alteration is located in exon 44 (coding exon 44) of the UNC13A gene. This alteration results from a G to C substitution at nucleotide position 4945, causing the alanine (A) at amino acid position 1649 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;D;T;T
Sift4G
Uncertain
D;D;D;D
Polyphen
B;.;.;.
Vest4
MutPred
Loss of catalytic residue at A1649 (P = 0.0056);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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
No publications associated with this variant yet.