dbSNP rs3746200: UNC13A:c.*4489A>G (chr19-17601565-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

18 publications found

Variant links:

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

UNC13A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001080421.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UNC13A	NM_001080421.3	MANE Select	c.*4489A>G	3_prime_UTR	Exon 44 of 44	NP_001073890.2	Q9UPW8
UNC13A	NM_001387021.1		c.*4489A>G	3_prime_UTR	Exon 42 of 42	NP_001373950.1
UNC13A	NM_001387022.1		c.*4489A>G	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.*4489A>G		3_prime_UTR	Exon 44 of 44	ENSP00000429562.2	Q9UPW8

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16836

AN:

152118

Hom.:

1085

Cov.:

show subpopulations

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:

AN:

204

Hom.:

Cov.:

AF XY:

0.130

AC XY:

AN XY:

138

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.114

AC:

AN:

202

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16844

AN:

152236

Hom.:

1085

Cov.:

AF XY:

0.109

AC XY:

8117

AN XY:

74448

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0938

AC:

6376

AN:

68008

Other (OTH)

AF:

0.111

AC:

235

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

749

1497

2246

2994

3743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.3

(source)

DANN

Benign

0.80

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over