15-54373855-C-T

Variant names:

• chr15-54373855-C-T
• rs12902248
• NM_001080534.3:c.4714-19193C>T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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

Gnomad4 AFR AF: 0.0532

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0603

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.170

Alfa AF: 0.139 Hom.: 231

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12902248; hg19: chr15-54666053;