15-54422555-G-T

Variant names:

• chr15-54422555-G-T
• rs11635375
• NM_001080534.3:c.4933+7488G>T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.4933+7488G>T		intron_variant	Intron 19 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.4933+7488G>T		intron_variant	Intron 19 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.4927+7488G>T		intron_variant	Intron 18 of 31			ENSP00000497525.1

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

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.251

Alfa AF: 0.198 Hom.: 863

Bravo AF: 0.260

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.71
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs11635375; hg19: chr15-54714753;