NM_001080534.3:c.4714-19193C>T

Variant names:

• chr15-54373855-C-T
• rs12902248
• NM_001080534.3:c.4714-19193C>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.4714-19193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,154 control chromosomes in the GnomAD database, including 1,590 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 0.13 (1590 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.4714-19193C>T		intron_variant	Intron 17 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.4714-19193C>T		intron_variant	Intron 17 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000561210.1	n.1289-19193C>T		intron_variant	Intron 9 of 11	1
UNC13C	ENST00000647821.1	c.4708-19193C>T		intron_variant	Intron 16 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20073 AN: 152036 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0604

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.132 AC: 20069 AN: 152154 Hom.: 1590 Cov.: 32 AF XY: 0.131 AC XY: 9714 AN XY: 74366

African (AFR) AF: 0.0532 AC: 2209 AN: 41528

American (AMR) AF: 0.181 AC: 2765 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3468

East Asian (EAS) AF: 0.0603 AC: 312 AN: 5172

South Asian (SAS) AF: 0.164 AC: 788 AN: 4810

European-Finnish (FIN) AF: 0.118 AC: 1243 AN: 10578

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11393 AN: 67994

Other (OTH) AF: 0.170 AC: 359 AN: 2108

Alfa AF: 0.137 Hom.: 234

Bravo AF: 0.134

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.26
PhyloP100		-1.3
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: rs12902248; hg19: chr15-54666053;