rs372260676

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001371189.2(UNC13B):​c.256C>A​(p.Arg86Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UNC13B
NM_001371189.2 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
UNC13B (HGNC:12566): (unc-13 homolog B) This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3180221).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNC13BNM_001371189.2 linkc.256C>A p.Arg86Ser missense_variant Exon 4 of 40 ENST00000635942.2 NP_001358118.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UNC13BENST00000635942.2 linkc.256C>A p.Arg86Ser missense_variant Exon 4 of 40 5 NM_001371189.2 ENSP00000490228.1 A0A1B0GUS7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461644
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Uncertain
0.071
D
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.075
.;T;.;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.4
M;.;.;M
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.5
.;N;.;N
REVEL
Benign
0.19
Sift
Benign
0.17
.;T;.;T
Sift4G
Benign
0.22
T;T;.;T
Polyphen
0.89
.;.;.;P
Vest4
0.60
MutPred
0.32
Gain of disorder (P = 0.0681);Gain of disorder (P = 0.0681);Gain of disorder (P = 0.0681);Gain of disorder (P = 0.0681);
MVP
0.66
MPC
0.36
ClinPred
0.95
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35236569; API