NM_001080534.3:c.3228+5268G>T

Variant names:

• chr15-54242958-G-T
• rs10518761
• NM_001080534.3:c.3228+5268G>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.3228+5268G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,986 control chromosomes in the GnomAD database, including 4,647 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 0.23 (4647 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 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.3228+5268G>T		intron	N/A	NP_001074003.1
	UNC13C	NM_001329919.2		c.3222+5268G>T		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.3228+5268G>T		intron	N/A	ENSP00000260323.11
	UNC13C	ENST00000647821.1		c.3222+5268G>T		intron	N/A	ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34202 AN: 151868 Hom.: 4637 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.225 AC: 34238 AN: 151986 Hom.: 4647 Cov.: 32 AF XY: 0.221 AC XY: 16431 AN XY: 74278

African (AFR) AF: 0.381 AC: 15766 AN: 41428

American (AMR) AF: 0.167 AC: 2542 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3468

East Asian (EAS) AF: 0.0547 AC: 283 AN: 5174

South Asian (SAS) AF: 0.103 AC: 498 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2108 AN: 10550

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11707 AN: 67966

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.179 Hom.: 4288

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.49
PhyloP100		-0.78
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: rs10518761; hg19: chr15-54535156;