rs10972365

Variant names:

• chr9-35168320-T-C
• rs10972365
• NM_001371189.2:c.22+6015T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371189.2(UNC13B):​c.22+6015T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,992 control chromosomes in the GnomAD database, including 3,320 homozygotes. 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: 𝑓 0.20 (3320 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

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.22+6015T>C		intron	N/A	NP_001358118.1	A0A1B0GUS7
	UNC13B	NM_001330653.3		c.22+6015T>C		intron	N/A	NP_001317582.1	O14795-2
	UNC13B	NM_001387551.1		c.22+6015T>C		intron	N/A	NP_001374480.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.22+6015T>C		intron	N/A	ENSP00000490228.1	A0A1B0GUS7
	UNC13B	ENST00000619578.4	TSL:1	c.22+6015T>C		intron	N/A	ENSP00000479261.1	O14795-2
	UNC13B	ENST00000378495.7	TSL:1	c.22+6015T>C		intron	N/A	ENSP00000367756.3	O14795-1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29754 AN: 151874 Hom.: 3319 Cov.: 31

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29760 AN: 151992 Hom.: 3320 Cov.: 31 AF XY: 0.193 AC XY: 14374 AN XY: 74290

African (AFR) AF: 0.0983 AC: 4076 AN: 41470

American (AMR) AF: 0.184 AC: 2804 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3466

East Asian (EAS) AF: 0.137 AC: 707 AN: 5166

South Asian (SAS) AF: 0.167 AC: 802 AN: 4804

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10544

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17547 AN: 67960

Other (OTH) AF: 0.206 AC: 434 AN: 2110

Alfa AF: 0.215 Hom.: 645

Bravo AF: 0.189

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.1
DANN	Benign	0.56
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10972365; hg19: chr9-35168317;