15-54576470-G-T

Variant names:

• chr15-54576470-G-T
• rs2553218
• NM_001080534.3:c.6106+8523G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080534.3(UNC13C):​c.6106+8523G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,032 control chromosomes in the GnomAD database, including 28,227 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 0.58 (28227 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.6106+8523G>T		intron_variant	Intron 30 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.6106+8523G>T		intron_variant	Intron 30 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.6100+8523G>T		intron_variant	Intron 29 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88736 AN: 151912 Hom.: 28161 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.585 AC: 88869 AN: 152032 Hom.: 28227 Cov.: 32 AF XY: 0.589 AC XY: 43770 AN XY: 74298

African (AFR) AF: 0.844 AC: 35024 AN: 41494

American (AMR) AF: 0.497 AC: 7583 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1379 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3490 AN: 5166

South Asian (SAS) AF: 0.593 AC: 2853 AN: 4814

European-Finnish (FIN) AF: 0.565 AC: 5970 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31078 AN: 67960

Other (OTH) AF: 0.507 AC: 1069 AN: 2108

Alfa AF: 0.500 Hom.: 29896

Bravo AF: 0.584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.79
DANN	Benign	0.33
PhyloP100		-0.17
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: rs2553218; hg19: chr15-54868668;