rs16953182

Positions:

• chr15-54281384-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13C	NM_001080534.3	c.3819-12511A>G		intron_variant		ENST00000260323.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13C	ENST00000260323.16	c.3819-12511A>G		intron_variant		5	NM_001080534.3	A1
UNC13C	ENST00000561210.1	n.394-12511A>G		intron_variant, non_coding_transcript_variant		1
UNC13C	ENST00000647821.1	c.3813-12511A>G		intron_variant				P4

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

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0474

Gnomad4 SAS AF: 0.0940

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.147

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.55

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: rs16953182; hg19: chr15-54573582;