rs12339582

Variant names:

• chr9-35398903-G-A
• rs12339582
• NM_001371189.2:c.11943G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-35398903-G-A
• chr9-35398903-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001371189.2(UNC13B):​c.11943G>A​(p.Glu3981Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UNC13B NM_001371189.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.043 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371189.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	NM_001371189.2	MANE Select	c.11943G>A	p.Glu3981Glu	synonymous	Exon 33 of 40	NP_001358118.1	A0A1B0GUS7
	UNC13B	NM_001371187.2		c.4836G>A	p.Glu1612Glu	synonymous	Exon 25 of 33	NP_001358116.1	A0A1B0GVW8
	UNC13B	NM_001387555.1		c.4833G>A	p.Glu1611Glu	synonymous	Exon 25 of 33	NP_001374484.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.11943G>A	p.Glu3981Glu	synonymous	Exon 33 of 40	ENSP00000490228.1	A0A1B0GUS7
	UNC13B	ENST00000619578.4	TSL:1	c.3696G>A	p.Glu1232Glu	synonymous	Exon 32 of 40	ENSP00000479261.1	O14795-2
	UNC13B	ENST00000378495.7	TSL:1	c.3696G>A	p.Glu1232Glu	synonymous	Exon 32 of 39	ENSP00000367756.3	O14795-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.8
DANN	Benign	0.52
PhyloP100		-0.043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12339582; hg19: chr9-35398900;