chr9-35295883-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001371189.2(UNC13B):c.714C>A(p.Asp238Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00943 in 1,613,968 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0077 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0096 ( 124 hom. )
Consequence
UNC13B
NM_001371189.2 missense
NM_001371189.2 missense
Scores
1
4
9
Clinical Significance
Conservation
PhyloP100: 1.82
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]
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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 (MetaRNN=0.0052330196).
BP6
?
Variant 9-35295883-C-A is Benign according to our data. Variant chr9-35295883-C-A is described in ClinVar as [Benign]. Clinvar id is 774465.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00961 (14047/1461696) while in subpopulation MID AF= 0.0333 (192/5768). AF 95% confidence interval is 0.0294. There are 124 homozygotes in gnomad4_exome. There are 7017 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC13B | NM_001371189.2 | c.714C>A | p.Asp238Glu | missense_variant | 8/40 | ENST00000635942.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC13B | ENST00000635942.2 | c.714C>A | p.Asp238Glu | missense_variant | 8/40 | 5 | NM_001371189.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00768 AC: 1168AN: 152154Hom.: 7 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00892 AC: 2238AN: 250888Hom.: 23 AF XY: 0.00881 AC XY: 1194AN XY: 135588
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GnomAD4 exome AF: 0.00961 AC: 14047AN: 1461696Hom.: 124 Cov.: 31 AF XY: 0.00965 AC XY: 7017AN XY: 727110
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GnomAD4 genome ? AF: 0.00766 AC: 1167AN: 152272Hom.: 7 Cov.: 32 AF XY: 0.00729 AC XY: 543AN XY: 74450
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ESP6500AA
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14
ESP6500EA
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124
ExAC
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952
Asia WGS
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8
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;.;T
Polyphen
0.88
.;.;.;P
Vest4
MutPred
Gain of catalytic residue at D238 (P = 0.1575);.;Gain of catalytic residue at D238 (P = 0.1575);Gain of catalytic residue at D238 (P = 0.1575);
MVP
MPC
0.26
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at