rs17183491

Variant names:

• chr15-53959858-T-C
• rs17183491
• XM_017022220.2:c.-257+41564T>C

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

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]

ENSG00000259669 (HGNC:):

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000658185.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000259669	ENST00000658185.1		n.89A>G		non_coding_transcript_exon	Exon 2 of 5
	ENSG00000259669	ENST00000557976.6	TSL:5	n.1521-4027A>G		intron	N/A
	ENSG00000259669	ENST00000558866.5	TSL:3	n.398-4027A>G		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17183491;

hg19: chr15-54252055;