rs7254755

Variant names:

• chr19-17605773-A-G
• rs7254755
• NM_001080421.3:c.*281T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

UNC13A Gene-Disease associations (from GenCC):

• congenital nervous system disorder

  Inheritance: Unknown Classification: LIMITED Submitted by: Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080421.3. 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
	UNC13A	NM_001080421.3	MANE Select	c.*281T>C		3_prime_UTR	Exon 44 of 44	NP_001073890.2	Q9UPW8
	UNC13A	NM_001387021.1		c.*281T>C		3_prime_UTR	Exon 42 of 42	NP_001373950.1
	UNC13A	NM_001387022.1		c.*281T>C		3_prime_UTR	Exon 42 of 42	NP_001373951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13A	ENST00000519716.7	TSL:5 MANE Select	c.*281T>C		3_prime_UTR	Exon 44 of 44	ENSP00000429562.2	Q9UPW8
	UNC13A	ENST00000551649.5	TSL:5	c.*281T>C		3_prime_UTR	Exon 45 of 45	ENSP00000447236.1	F8W059
	UNC13A	ENST00000552293.5	TSL:5	c.*281T>C		downstream_gene	N/A	ENSP00000447572.1	F8W0P6

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

African (AFR) AF: 0.126 AC: 714 AN: 5688

American (AMR) AF: 0.155 AC: 859 AN: 5526

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 2166 AN: 7940

East Asian (EAS) AF: 0.000409 AC: 7 AN: 17116

South Asian (SAS) AF: 0.110 AC: 1182 AN: 10778

European-Finnish (FIN) AF: 0.212 AC: 4175 AN: 19660

Middle Eastern (MID) AF: 0.240 AC: 286 AN: 1194

European-Non Finnish (NFE) AF: 0.257 AC: 37884 AN: 147632

Other (OTH) AF: 0.226 AC: 3368 AN: 14926

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

African (AFR) AF: 0.122 AC: 5055 AN: 41516

American (AMR) AF: 0.179 AC: 2740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3472

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5154

South Asian (SAS) AF: 0.105 AC: 509 AN: 4828

European-Finnish (FIN) AF: 0.213 AC: 2253 AN: 10594

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 18074 AN: 67950

Other (OTH) AF: 0.211 AC: 445 AN: 2108

Alfa AF: 0.249 Hom.: 4488

Bravo AF: 0.193

Asia WGS AF: 0.0650 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.0
DANN	Benign	0.85
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7254755; hg19: chr19-17716582;