19-17652081-G-A

Position:

• chr19-17652081-G-A

Variant summary

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

The NM_001080421.3(UNC13A):​c.1439+550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,676 control chromosomes in the GnomAD database, including 35,896 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 0.68 (35896 hom., cov: 31)
• Consequence: UNC13A NM_001080421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13A	NM_001080421.3	c.1439+550C>T		intron_variant		ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13A	ENST00000519716.7	c.1439+550C>T		intron_variant		5	NM_001080421.3	ENSP00000429562	A2
UNC13A	ENST00000550896.1	c.1439+550C>T		intron_variant		5		ENSP00000446831	A2
UNC13A	ENST00000551649.5	c.1439+550C>T		intron_variant		5		ENSP00000447236	P3
UNC13A	ENST00000552293.5	c.1439+550C>T		intron_variant		5		ENSP00000447572	A2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102942 AN: 151560 Hom.: 35870 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.646

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.679 AC: 103016 AN: 151676 Hom.: 35896 Cov.: 31 AF XY: 0.680 AC XY: 50374 AN XY: 74092

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.640

Alfa AF: 0.617 Hom.: 49288

Bravo AF: 0.677

Asia WGS AF: 0.683 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.60

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: rs10416963; hg19: chr19-17762890;