15-54001072-A-G

Position:

• chr15-54001072-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080534.3(UNC13C):​c.-256-11576A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,952 control chromosomes in the GnomAD database, including 26,889 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 0.57 (26889 hom., cov: 31)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.-256-11576A>G		intron_variant		ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.-256-11576A>G		intron_variant		5	NM_001080534.3	ENSP00000260323	A1
UNC13C	ENST00000647821.1	c.-256-11576A>G		intron_variant				ENSP00000497525	P4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86588 AN: 151834 Hom.: 26901 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.570 AC: 86576 AN: 151952 Hom.: 26889 Cov.: 31 AF XY: 0.567 AC XY: 42118 AN XY: 74274

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.622

Alfa AF: 0.593 Hom.: 4283

Bravo AF: 0.562

Asia WGS AF: 0.492 AC: 1714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12912451; hg19: chr15-54293269;