rs372260676

Variant names:

• chr9-35236572-C-A
• NM_001371189.2:c.256C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-35236572-C-A
• chr9-35236572-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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]

ACMG classification

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
UNC13B	NM_001371189.2	c.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
UNC13B	ENST00000635942.2	c.256C>A	p.Arg86Ser	missense_variant	Exon 4 of 40	5	NM_001371189.2	ENSP00000490228.1

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

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;