rs1897031

Positions:

• chr15-54049268-G-A
• chr15-54049268-G-C

Variant summary

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

The NM_001080534.3(UNC13C):​c.2983+33382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 527,576 control chromosomes in the GnomAD database, including 184,710 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 0.84 (54420 hom., cov: 33)
  • Exomes 𝑓: 0.83 (130290 hom.)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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]

ENSG00000259619 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.2983+33382G>A		intron_variant		ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.2983+33382G>A		intron_variant		5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.2983+33382G>A		intron_variant				ENSP00000497525.1
ENSG00000259619	ENST00000558038.2	n.1609C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128388 AN: 152110 Hom.: 54368 Cov.: 33

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.855

GnomAD4 exome AF: 0.831 AC: 311856 AN: 375348 Hom.: 130290 Cov.: 0 AF XY: 0.832 AC XY: 177420 AN XY: 213236

Gnomad4 AFR exome AF: 0.890

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.811

Gnomad4 FIN exome AF: 0.815

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.846

GnomAD4 genome AF: 0.844 AC: 128496 AN: 152228 Hom.: 54420 Cov.: 33 AF XY: 0.839 AC XY: 62434 AN XY: 74414

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.857

Alfa AF: 0.854 Hom.: 101955

Bravo AF: 0.844

Asia WGS AF: 0.774 AC: 2694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.97
DANN	Benign	0.76

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: rs1897031; hg19: chr15-54341465; COSMIC: COSV52853662;