15-54070280-T-G

Variant names:

• chr15-54070280-T-G
• rs11071022
• NM_001080534.3:c.2983+54394T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080534.3(UNC13C):​c.2983+54394T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,136 control chromosomes in the GnomAD database, including 19,038 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 0.48 (19038 hom., cov: 33)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 3 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080534.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	NM_001080534.3	MANE Select	c.2983+54394T>G		intron	N/A	NP_001074003.1
	UNC13C	NM_001329919.2		c.2983+54394T>G		intron	N/A	NP_001316848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	ENST00000260323.16	TSL:5 MANE Select	c.2983+54394T>G		intron	N/A	ENSP00000260323.11
	UNC13C	ENST00000647821.1		c.2983+54394T>G		intron	N/A	ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72783 AN: 152018 Hom.: 19041 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.478 AC: 72783 AN: 152136 Hom.: 19038 Cov.: 33 AF XY: 0.476 AC XY: 35419 AN XY: 74370

African (AFR) AF: 0.262 AC: 10882 AN: 41530

American (AMR) AF: 0.476 AC: 7267 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2395 AN: 5174

South Asian (SAS) AF: 0.482 AC: 2326 AN: 4824

European-Finnish (FIN) AF: 0.567 AC: 5984 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39954 AN: 67984

Other (OTH) AF: 0.508 AC: 1071 AN: 2110

Alfa AF: 0.553 Hom.: 100827

Bravo AF: 0.461

Asia WGS AF: 0.447 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.6
DANN	Benign	0.85
PhyloP100		0.56
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: rs11071022; hg19: chr15-54362477;