Variant 9-35231197-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371189.2(UNC13B):c.130T>G(p.Ser44Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,762 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

UNC13B
NM_001371189.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

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]

UNC13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25328848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13B	NM_001371189.2 linkuse as main transcript	c.130T>G	p.Ser44Ala	missense_variant	3/40	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2 linkuse as main transcript	c.130T>G	p.Ser44Ala	missense_variant	3/40	5	NM_001371189.2	ENSP00000490228

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726720

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

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

Jan 26, 2022

The c.130T>G (p.S44A) alteration is located in exon 3 (coding exon 3) of the UNC13B gene. This alteration results from a T to G substitution at nucleotide position 130, causing the serine (S) at amino acid position 44 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.043

.;T;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.63

.;N;.;N

REVEL

Benign

0.14

Sift

Benign

1.0

.;T;.;T

Sift4G

Benign

0.27

T;T;.;T

Polyphen

0.0020

.;.;.;B

Vest4

0.37

MutPred

0.48

Gain of catalytic residue at S44 (P = 0.0014);Gain of catalytic residue at S44 (P = 0.0014);Gain of catalytic residue at S44 (P = 0.0014);Gain of catalytic residue at S44 (P = 0.0014);

MVP

0.51

MPC

0.17

ClinPred

0.62

GERP RS

2.8

Varity_R

0.054

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over