rs16953182

Variant names:

• chr15-54281384-A-G
• rs16953182
• NM_001080534.3:c.3819-12511A>G

Variant summary

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

The NM_001080534.3(UNC13C):​c.3819-12511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,194 control chromosomes in the GnomAD database, including 2,455 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 0.17 (2455 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 2 publications found

Genes affected

UNC13C (HGNC:23149): (unc-13 homolog C) Predicted to enable calmodulin binding activity and syntaxin-1 binding activity. Predicted to be involved in several processes, including glutamatergic synaptic transmission; regulated exocytosis; and synaptic vesicle maturation. Predicted to be located in presynaptic active zone. Predicted to be active in several cellular components, including axon terminus; parallel fiber to Purkinje cell synapse; and presynaptic active zone cytoplasmic component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080534.3. 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
	UNC13C	NM_001080534.3	MANE Select	c.3819-12511A>G		intron	N/A	NP_001074003.1
	UNC13C	NM_001329919.2		c.3813-12511A>G		intron	N/A	NP_001316848.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	ENST00000260323.16	TSL:5 MANE Select	c.3819-12511A>G		intron	N/A	ENSP00000260323.11
	UNC13C	ENST00000561210.1	TSL:1	n.394-12511A>G		intron	N/A
	UNC13C	ENST00000647821.1		c.3813-12511A>G		intron	N/A	ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25313 AN: 152076 Hom.: 2450 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.166 AC: 25340 AN: 152194 Hom.: 2455 Cov.: 32 AF XY: 0.163 AC XY: 12117 AN XY: 74390

African (AFR) AF: 0.259 AC: 10743 AN: 41514

American (AMR) AF: 0.139 AC: 2128 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.0474 AC: 245 AN: 5166

South Asian (SAS) AF: 0.0940 AC: 454 AN: 4828

European-Finnish (FIN) AF: 0.139 AC: 1471 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9305 AN: 68018

Other (OTH) AF: 0.147 AC: 312 AN: 2116

Alfa AF: 0.146 Hom.: 375

Bravo AF: 0.170

Asia WGS AF: 0.0930 AC: 323 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.10
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: rs16953182; hg19: chr15-54573582;