chr15-54242958-G-T

Position:

• chr15-54242958-G-T

Variant summary

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

The NM_001080534.3(UNC13C):​c.3228+5268G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,986 control chromosomes in the GnomAD database, including 4,647 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 0.23 (4647 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.3228+5268G>T		intron_variant		ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.3228+5268G>T		intron_variant		5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.3222+5268G>T		intron_variant				ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34202 AN: 151868 Hom.: 4637 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.225 AC: 34238 AN: 151986 Hom.: 4647 Cov.: 32 AF XY: 0.221 AC XY: 16431 AN XY: 74278

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.202

Alfa AF: 0.172 Hom.: 3067

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.49

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: rs10518761; hg19: chr15-54535156;