rs7254755

Positions:

• chr19-17605773-A-G

Variant summary

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

The NM_001080421.3(UNC13A):​c.*281T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 382,570 control chromosomes in the GnomAD database, including 9,903 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 0.20 (3433 hom., cov: 33)
  • Exomes 𝑓: 0.22 (6470 hom.)
• Consequence: UNC13A NM_001080421.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

Genes affected

UNC13A (HGNC:23150): (unc-13 homolog A) This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13A	NM_001080421.3	c.*281T>C		3_prime_UTR_variant	44/44	ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13A	ENST00000519716.7	c.*281T>C		3_prime_UTR_variant	44/44	5	NM_001080421.3	ENSP00000429562	A2
UNC13A	ENST00000551649.5	c.*281T>C		3_prime_UTR_variant	45/45	5		ENSP00000447236	P3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30342 AN: 151990 Hom.: 3433 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.220 AC: 50641 AN: 230460 Hom.: 6470 Cov.: 2 AF XY: 0.219 AC XY: 25831 AN XY: 118062

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.000409

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.200 AC: 30350 AN: 152110 Hom.: 3433 Cov.: 33 AF XY: 0.194 AC XY: 14449 AN XY: 74372

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.211

Alfa AF: 0.258 Hom.: 3739

Bravo AF: 0.193

Asia WGS AF: 0.0650 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.0
DANN	Benign	0.85

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: rs7254755; hg19: chr19-17716582;