chr15-54422285-T-G

Variant names:

• chr15-54422285-T-G
• rs10444833
• NM_001080534.3:c.4933+7218T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080534.3(UNC13C):​c.4933+7218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,858 control chromosomes in the GnomAD database, including 5,270 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 0.26 (5270 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.4933+7218T>G		intron_variant	Intron 19 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.4933+7218T>G		intron_variant	Intron 19 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.4927+7218T>G		intron_variant	Intron 18 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39226 AN: 151740 Hom.: 5258 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.259 AC: 39291 AN: 151858 Hom.: 5270 Cov.: 32 AF XY: 0.260 AC XY: 19306 AN XY: 74234

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.255

Alfa AF: 0.218 Hom.: 1489

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.4
DANN	Benign	0.88

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: rs10444833; hg19: chr15-54714483;