rs3746200

chr19-17601565-T-C

Variant summary

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

The NM_001080421.3(UNC13A):c.*4489A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,440 control chromosomes in the GnomAD database, including 1,088 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 0.11 (1085 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: UNC13A NM_001080421.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13A	NM_001080421.3	c.*4489A>G		3_prime_UTR_variant	44/44	ENST00000519716.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13A	ENST00000519716.7	c.*4489A>G		3_prime_UTR_variant	44/44	5	NM_001080421.3	A2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16836 AN: 152118 Hom.: 1085 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.118 AC: 24 AN: 204 Hom.: 3 Cov.: 0 AF XY: 0.130 AC XY: 18 AN XY: 138

Gnomad4 FIN exome AF: 0.114

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.111 AC: 16844 AN: 152236 Hom.: 1085 Cov.: 32 AF XY: 0.109 AC XY: 8117 AN XY: 74448

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.0586

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.0938

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0961 Hom.: 1091

Bravo AF: 0.110

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.3
Dann	Benign	0.80

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: rs3746200; hg19: chr19-17712374;