15-54049268-G-A

Variant names:

• chr15-54049268-G-A
• rs1897031
• NM_001080534.3:c.2983+33382G>A

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+33382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 527,576 control chromosomes in the GnomAD database, including 184,710 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 0.84 (54420 hom., cov: 33)
  • Exomes 𝑓: 0.83 (130290 hom.)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 13 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]

ENSG00000259619 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 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+33382G>A		intron	N/A	NP_001074003.1
	UNC13C	NM_001329919.2		c.2983+33382G>A		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+33382G>A		intron	N/A	ENSP00000260323.11
	ENSG00000259619	ENST00000558038.2	TSL:6	n.1609C>T		non_coding_transcript_exon	Exon 1 of 1
	UNC13C	ENST00000647821.1		c.2983+33382G>A		intron	N/A	ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128388 AN: 152110 Hom.: 54368 Cov.: 33

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.855

GnomAD4 exome AF: 0.831 AC: 311856 AN: 375348 Hom.: 130290 Cov.: 0 AF XY: 0.832 AC XY: 177420 AN XY: 213236

African (AFR) AF: 0.890 AC: 8561 AN: 9624

American (AMR) AF: 0.706 AC: 20957 AN: 29690

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 9898 AN: 11472

East Asian (EAS) AF: 0.675 AC: 9478 AN: 14032

South Asian (SAS) AF: 0.811 AC: 49398 AN: 60902

European-Finnish (FIN) AF: 0.815 AC: 25688 AN: 31500

Middle Eastern (MID) AF: 0.859 AC: 1490 AN: 1734

European-Non Finnish (NFE) AF: 0.863 AC: 171903 AN: 199266

Other (OTH) AF: 0.846 AC: 14483 AN: 17128

GnomAD4 genome AF: 0.844 AC: 128496 AN: 152228 Hom.: 54420 Cov.: 33 AF XY: 0.839 AC XY: 62434 AN XY: 74414

African (AFR) AF: 0.876 AC: 36403 AN: 41544

American (AMR) AF: 0.765 AC: 11701 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2993 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3489 AN: 5166

South Asian (SAS) AF: 0.813 AC: 3915 AN: 4818

European-Finnish (FIN) AF: 0.805 AC: 8525 AN: 10596

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58552 AN: 68020

Other (OTH) AF: 0.857 AC: 1812 AN: 2114

Alfa AF: 0.852 Hom.: 233675

Bravo AF: 0.844

Asia WGS AF: 0.774 AC: 2694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.97
DANN	Benign	0.76
PhyloP100		2.6
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: rs1897031; hg19: chr15-54341465; COSMIC: COSV52853662;