rs17183491

Variant names:

• chr15-53959858-T-C
• rs17183491
• ENST00000658185.1:n.89A>G

Variant summary

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

The ENST00000658185.1(ENSG00000259669):​n.89A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,140 control chromosomes in the GnomAD database, including 3,247 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 0.17 (3247 hom., cov: 32)
• Consequence: ENSG00000259669 ENST00000658185.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 1 publications found

Genes affected

ENSG00000259669 (HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	XM_017022220.2	c.-257+41564T>C		intron_variant	Intron 5 of 36		XP_016877709.1
UNC13C	XM_017022221.2	c.-257+41564T>C		intron_variant	Intron 4 of 35		XP_016877710.1
UNC13C	XM_017022222.2	c.-256-52790T>C		intron_variant	Intron 3 of 34		XP_016877711.1
UNC13C	XM_047432538.1	c.-257+41564T>C		intron_variant	Intron 6 of 37		XP_047288494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000259669	ENST00000658185.1	n.89A>G		non_coding_transcript_exon_variant	Exon 2 of 5
ENSG00000259669	ENST00000557976.6	n.1521-4027A>G		intron_variant	Intron 5 of 6	5
ENSG00000259669	ENST00000558866.5	n.398-4027A>G		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25962 AN: 152022 Hom.: 3247 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.171 AC: 25987 AN: 152140 Hom.: 3247 Cov.: 32 AF XY: 0.176 AC XY: 13060 AN XY: 74380

African (AFR) AF: 0.327 AC: 13552 AN: 41480

American (AMR) AF: 0.0943 AC: 1443 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2016 AN: 5160

South Asian (SAS) AF: 0.192 AC: 923 AN: 4816

European-Finnish (FIN) AF: 0.178 AC: 1886 AN: 10586

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5538 AN: 68012

Other (OTH) AF: 0.145 AC: 307 AN: 2112

Alfa AF: 0.118 Hom.: 3107

Bravo AF: 0.172

Asia WGS AF: 0.286 AC: 990 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.84
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17183491; hg19: chr15-54252055;