Genetic Variant UNC13C:c.2983+33382G>C (chr15-54049268-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080534.3(UNC13C):c.2983+33382G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UNC13C
NM_001080534.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56

Publications

13 publications found

Variant links:

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]

UNC13C links:

ENSG00000259619 (HGNC:):

ENSG00000259619 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3 link	c.2983+33382G>C		intron_variant	Intron 2 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
UNC13C	ENST00000260323.16 link	c.2983+33382G>C	intron_variant	Intron 2 of 32	5	NM_001080534.3	ENSP00000260323.11
ENSG00000259619	ENST00000558038.2 link	n.1609C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
UNC13C	ENST00000647821.1 link	c.2983+33382G>C	intron_variant	Intron 2 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

375676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

213426

African (AFR)

AF:

0.00

AC:

AN:

9642

American (AMR)

AF:

0.00

AC:

AN:

29730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11482

East Asian (EAS)

AF:

0.00

AC:

AN:

14056

South Asian (SAS)

AF:

0.00

AC:

AN:

60964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

199400

Other (OTH)

AF:

0.00

AC:

AN:

17146

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.72

(source)

DANN

Benign

0.63

PhyloP100

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over