NM_001080421.3:c.1439+550C>T

Variant names:

• chr19-17652081-G-A
• rs10416963
• NM_001080421.3:c.1439+550C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-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 rank	MANE	Protein	UniProt
UNC13A	NM_001080421.3	c.1439+550C>T		intron_variant	Intron 12 of 43	ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13A	ENST00000519716.7	c.1439+550C>T		intron_variant	Intron 12 of 43	5	NM_001080421.3	ENSP00000429562.2
UNC13A	ENST00000551649.5	c.1439+550C>T		intron_variant	Intron 12 of 44	5		ENSP00000447236.1
UNC13A	ENST00000552293.5	c.1439+550C>T		intron_variant	Intron 12 of 41	5		ENSP00000447572.1
UNC13A	ENST00000550896.1	c.1439+550C>T		intron_variant	Intron 12 of 39	5		ENSP00000446831.1

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

African (AFR) AF: 0.854 AC: 35352 AN: 41380

American (AMR) AF: 0.583 AC: 8893 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2257 AN: 3464

East Asian (EAS) AF: 0.691 AC: 3552 AN: 5142

South Asian (SAS) AF: 0.675 AC: 3252 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6819 AN: 10490

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.603 AC: 40921 AN: 67832

Other (OTH) AF: 0.640 AC: 1343 AN: 2098

Alfa AF: 0.629 Hom.: 118253

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
PhyloP100		-0.40
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: rs10416963; hg19: chr19-17762890;