rs10518772

Variant names:

• chr15-54575663-C-T
• rs10518772
• NM_001080534.3:c.6106+7716C>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.6106+7716C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,064 control chromosomes in the GnomAD database, including 162 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 0.035 (162 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.6106+7716C>T		intron_variant	Intron 30 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.6106+7716C>T		intron_variant	Intron 30 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.6100+7716C>T		intron_variant	Intron 29 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5254 AN: 151960 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0408

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

GnomAD4 genome AF: 0.0346 AC: 5254 AN: 152064 Hom.: 162 Cov.: 32 AF XY: 0.0363 AC XY: 2694 AN XY: 74310

African (AFR) AF: 0.0632 AC: 2622 AN: 41494

American (AMR) AF: 0.0223 AC: 341 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3466

East Asian (EAS) AF: 0.115 AC: 592 AN: 5158

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4814

European-Finnish (FIN) AF: 0.0488 AC: 514 AN: 10536

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 769 AN: 68010

Other (OTH) AF: 0.0404 AC: 85 AN: 2102

Alfa AF: 0.0217 Hom.: 25

Bravo AF: 0.0346

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		0.20
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: rs10518772; hg19: chr15-54867861;