NM_001080534.3:c.2983+53621C>T

Variant names:

• chr15-54069507-C-T
• rs11636091
• NM_001080534.3:c.2983+53621C>T

Variant summary

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

The NM_001080534.3(UNC13C):​c.2983+53621C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,232 control chromosomes in the GnomAD database, including 290 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 0.051 (290 hom., cov: 33)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0788 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.2983+53621C>T		intron	N/A	NP_001074003.1	Q8NB66
	UNC13C	NM_001329919.2		c.2983+53621C>T		intron	N/A	NP_001316848.1	A0A3B3ISZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	ENST00000260323.16	TSL:5 MANE Select	c.2983+53621C>T		intron	N/A	ENSP00000260323.11	Q8NB66
	UNC13C	ENST00000647821.1		c.2983+53621C>T		intron	N/A	ENSP00000497525.1	A0A3B3ISZ1

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7691 AN: 152114 Hom.: 290 Cov.: 33

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0505 AC: 7693 AN: 152232 Hom.: 290 Cov.: 33 AF XY: 0.0517 AC XY: 3849 AN XY: 74430

African (AFR) AF: 0.0123 AC: 513 AN: 41558

American (AMR) AF: 0.0336 AC: 513 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0856 AC: 413 AN: 4822

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10592

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4785 AN: 67998

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0440 Hom.: 62

Bravo AF: 0.0426

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.76
PhyloP100		0.086
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: rs11636091; hg19: chr15-54361704;