rs10518748

chr15-53989784-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UNC13C	NM_001080534.3	c.-257+10857G>A		intron_variant		ENST00000260323.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13C	ENST00000260323.16	c.-257+10857G>A		intron_variant		5	NM_001080534.3	A1
UNC13C	ENST00000647821.1	c.-257+10857G>A		intron_variant				P4

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

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.0299

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0289 Hom.: 21

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518748; hg19: chr15-54281981;