chr19-17601565-T-C

Variant names:

• chr19-17601565-T-C
• rs3746200
• NM_001080421.3:c.*4489A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UNC13A	NM_001080421.3	c.*4489A>G		3_prime_UTR_variant	Exon 44 of 44	ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13A	ENST00000519716.7	c.*4489A>G		3_prime_UTR_variant	Exon 44 of 44	5	NM_001080421.3	ENSP00000429562.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.114 AC: 23 AN: 202

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.174 AC: 7220 AN: 41524

American (AMR) AF: 0.0795 AC: 1215 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.0152 AC: 79 AN: 5184

South Asian (SAS) AF: 0.0586 AC: 283 AN: 4832

European-Finnish (FIN) AF: 0.0983 AC: 1043 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6376 AN: 68008

Other (OTH) AF: 0.111 AC: 235 AN: 2108

Alfa AF: 0.0981 Hom.: 1413

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
PhyloP100		-2.2
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: rs3746200; hg19: chr19-17712374;