NM_001080534.3:c.4933+7488G>T

Variant names:

• chr15-54422555-G-T
• rs11635375
• NM_001080534.3:c.4933+7488G>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.4933+7488G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,648 control chromosomes in the GnomAD database, including 5,034 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 0.25 (5034 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	NM_001080534.3	MANE Select	c.4933+7488G>T		intron	N/A	NP_001074003.1	Q8NB66
	UNC13C	NM_001329919.2		c.4927+7488G>T		intron	N/A	NP_001316848.1	A0A3B3ISZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	ENST00000260323.16	TSL:5 MANE Select	c.4933+7488G>T		intron	N/A	ENSP00000260323.11	Q8NB66
	UNC13C	ENST00000647821.1		c.4927+7488G>T		intron	N/A	ENSP00000497525.1	A0A3B3ISZ1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38452 AN: 151530 Hom.: 5023 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.254 AC: 38511 AN: 151648 Hom.: 5034 Cov.: 32 AF XY: 0.255 AC XY: 18879 AN XY: 74082

African (AFR) AF: 0.301 AC: 12452 AN: 41356

American (AMR) AF: 0.295 AC: 4484 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1401 AN: 5108

South Asian (SAS) AF: 0.199 AC: 957 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2449 AN: 10522

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15491 AN: 67862

Other (OTH) AF: 0.251 AC: 528 AN: 2100

Alfa AF: 0.212 Hom.: 1479

Bravo AF: 0.260

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.71
DANN	Benign	0.47
PhyloP100		-0.12
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: rs11635375; hg19: chr15-54714753;