dbSNP rs7254755: UNC13A:c.*281T>C (chr19-17605773-A-G) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

6 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

UNC13A links:

Genome browser will be placed here

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=-0.7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13A	NM_001080421.3 link	c.*281T>C		3_prime_UTR_variant	Exon 44 of 44	ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UNC13A	ENST00000519716.7 link	c.*281T>C	3_prime_UTR_variant	Exon 44 of 44	5	NM_001080421.3	ENSP00000429562.2	Q9UPW8
UNC13A	ENST00000551649.5 link	c.*281T>C	3_prime_UTR_variant	Exon 45 of 45	5		ENSP00000447236.1	F8W059
UNC13A	ENST00000552293.5 link	c.*281T>C	downstream_gene_variant		5		ENSP00000447572.1	F8W0P6

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30342

AN:

151990

Hom.:

3433

Cov.:

show subpopulations

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.:

AF XY:

0.219

AC XY:

25831

AN XY:

118062

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1745

3489

5234

6978

8723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30350

AN:

152110

Hom.:

3433

Cov.:

AF XY:

0.194

AC XY:

14449

AN XY:

74372

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18074

AN:

67950

Other (OTH)

AF:

0.211

AC:

445

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1271

2542

3812

5083

6354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.249

Hom.:

4488

Bravo

AF:

0.193

Asia WGS

AF:

0.0650

AC:

230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.0

(source)

DANN

Benign

0.85

PhyloP100

0.031

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over