NM_001080534.3:c.4714-4614A>C

Variant names:

• chr15-54388434-A-C
• rs10518765
• NM_001080534.3:c.4714-4614A>C

Variant summary

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

The NM_001080534.3(UNC13C):​c.4714-4614A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,106 control chromosomes in the GnomAD database, including 2,187 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 0.16 (2187 hom., cov: 31)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	NM_001080534.3	MANE Select	c.4714-4614A>C		intron	N/A	NP_001074003.1
	UNC13C	NM_001329919.2		c.4708-4614A>C		intron	N/A	NP_001316848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	ENST00000260323.16	TSL:5 MANE Select	c.4714-4614A>C		intron	N/A	ENSP00000260323.11
	UNC13C	ENST00000561210.1	TSL:1	n.1289-4614A>C		intron	N/A
	UNC13C	ENST00000647821.1		c.4708-4614A>C		intron	N/A	ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24320 AN: 151988 Hom.: 2186 Cov.: 31

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.160 AC: 24322 AN: 152106 Hom.: 2187 Cov.: 31 AF XY: 0.159 AC XY: 11795 AN XY: 74354

African (AFR) AF: 0.0826 AC: 3430 AN: 41526

American (AMR) AF: 0.184 AC: 2806 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 748 AN: 3472

East Asian (EAS) AF: 0.0616 AC: 318 AN: 5164

South Asian (SAS) AF: 0.171 AC: 822 AN: 4814

European-Finnish (FIN) AF: 0.169 AC: 1787 AN: 10598

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13662 AN: 67968

Other (OTH) AF: 0.195 AC: 413 AN: 2114

Alfa AF: 0.191 Hom.: 12749

Bravo AF: 0.159

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		0.34
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: rs10518765; hg19: chr15-54680632;