chr15-53989784-G-A

Variant names:

• chr15-53989784-G-A
• rs10518748
• NM_001080534.3:c.-257+10857G>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.-257+10857G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 151,946 control chromosomes in the GnomAD database, including 359 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 0.047 (359 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.-257+10857G>A		intron_variant	Intron 1 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.-257+10857G>A		intron_variant	Intron 1 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.-257+10857G>A		intron_variant	Intron 1 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7056 AN: 151828 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0467 AC: 7091 AN: 151946 Hom.: 359 Cov.: 32 AF XY: 0.0515 AC XY: 3826 AN XY: 74292

African (AFR) AF: 0.0824 AC: 3418 AN: 41466

American (AMR) AF: 0.0299 AC: 456 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.205 AC: 1054 AN: 5136

South Asian (SAS) AF: 0.119 AC: 573 AN: 4810

European-Finnish (FIN) AF: 0.0774 AC: 820 AN: 10588

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0100 AC: 681 AN: 67920

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0308 Hom.: 24

Bravo AF: 0.0430

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0060
DANN	Benign	0.51
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10518748; hg19: chr15-54281981;