10-49612378-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003055.3(SLC18A3):c.*39G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,544,970 control chromosomes in the GnomAD database, including 13,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1667 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12042 hom. )

Consequence

SLC18A3
NM_003055.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.84

Publications

11 publications found

Variant links:

Genes affected

SLC18A3 (HGNC:10936): (solute carrier family 18 member A3) This gene is a member of the vesicular amine transporter family. The encoded transmembrane protein transports acetylcholine into secretory vesicles for release into the extracellular space. Acetylcholine transport utilizes a proton gradient established by a vacuolar ATPase. This gene is located within the first intron of the choline acetyltransferase gene. [provided by RefSeq, Jul 2008]

SLC18A3 links:

CHAT (HGNC:1912): (choline O-acetyltransferase) This gene encodes an enzyme which catalyzes the biosynthesis of the neurotransmitter acetylcholine. This gene product is a characteristic feature of cholinergic neurons, and changes in these neurons may explain some of the symptoms of Alzheimer's disease. Polymorphisms in this gene have been associated with Alzheimer's disease and mild cognitive impairment. Mutations in this gene are associated with congenital myasthenic syndrome associated with episodic apnea. Multiple transcript variants encoding different isoforms have been found for this gene, and some of these variants have been shown to encode more than one isoform. [provided by RefSeq, May 2010]

CHAT Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 6
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-49612378-G-T is Benign according to our data. Variant chr10-49612378-G-T is described in ClinVar as Benign. ClinVar VariationId is 1175691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A3	NM_003055.3 link	c.*39G>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000374115.5	NP_003046.2
CHAT	NM_020984.4 link	c.-69+3179G>T		intron_variant	Intron 1 of 14		NP_066264.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A3	ENST00000374115.5 link	c.*39G>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_003055.3	ENSP00000363229.3
CHAT	ENST00000339797.5 link	c.-69+3179G>T		intron_variant	Intron 1 of 14	1		ENSP00000343486.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19787

AN:

151986

Hom.:

1666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.0913

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.132

GnomAD2 exomes

AF:

0.163

AC:

32571

AN:

199974

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.474

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.119

AC:

165873

AN:

1392866

Hom.:

12042

Cov.:

AF XY:

0.117

AC XY:

80303

AN XY:

684014

show subpopulations

African (AFR)

AF:

0.101

AC:

3219

AN:

31750

American (AMR)

AF:

0.191

AC:

7262

AN:

37950

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

2900

AN:

21860

East Asian (EAS)

AF:

0.397

AC:

15468

AN:

38990

South Asian (SAS)

AF:

0.0888

AC:

6627

AN:

74614

European-Finnish (FIN)

AF:

0.197

AC:

9864

AN:

50100

Middle Eastern (MID)

AF:

0.116

AC:

630

AN:

5452

European-Non Finnish (NFE)

AF:

0.105

AC:

112581

AN:

1074766

Other (OTH)

AF:

0.128

AC:

7322

AN:

57384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

7795

15590

23386

31181

38976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4454

8908

13362

17816

22270

<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:

0.130

AC:

19796

AN:

152104

Hom.:

1667

Cov.:

AF XY:

0.135

AC XY:

10028

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.106

AC:

4402

AN:

41496

American (AMR)

AF:

0.139

AC:

2130

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

450

AN:

3468

East Asian (EAS)

AF:

0.451

AC:

2324

AN:

5152

South Asian (SAS)

AF:

0.0911

AC:

440

AN:

4828

European-Finnish (FIN)

AF:

0.206

AC:

2177

AN:

10566

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7471

AN:

67996

Other (OTH)

AF:

0.132

AC:

279

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

851

1701

2552

3402

4253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.115

Hom.:

625

Bravo

AF:

0.130

Asia WGS

AF:

0.247

AC:

858

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

1.8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over