10-49610777-G-C

Position:

chr10-49610777-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003055.3(SLC18A3):c.37G>C(p.Ala13Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,565,116 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 34)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SLC18A3
NM_003055.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.45

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060650706).

BP6

Variant 10-49610777-G-C is Benign according to our data. Variant chr10-49610777-G-C is described in ClinVar as [Benign]. Clinvar id is 717239.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A3	NM_003055.3 linkuse as main transcript	c.37G>C	p.Ala13Pro	missense_variant	1/1	ENST00000374115.5	NP_003046.2	Q16572
CHAT	NM_020984.4 linkuse as main transcript	c.-69+1578G>C		intron_variant			NP_066264.4	P28329-3D3DX95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A3	ENST00000374115.5 linkuse as main transcript	c.37G>C	p.Ala13Pro	missense_variant	1/1	6	NM_003055.3	ENSP00000363229.3		Q16572
CHAT	ENST00000339797.5 linkuse as main transcript	c.-69+1578G>C		intron_variant		1		ENSP00000343486.1		P28329-3

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

484

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000523

AC:

AN:

173888

Hom.:

AF XY:

0.000276

AC XY:

AN XY:

94348

show subpopulations

Gnomad AFR exome

AF:

0.00694

Gnomad AMR exome

AF:

0.000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000430

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000135

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000274

AC:

387

AN:

1412732

Hom.:

Cov.:

AF XY:

0.000225

AC XY:

157

AN XY:

699086

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.000395

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.18e-7

Gnomad4 OTH exome

AF:

0.000616

GnomAD4 genome

AF:

0.00324

AC:

494

AN:

152384

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00377

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000333

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.0

REVEL

Benign

0.27

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.41

MVP

0.51

ClinPred

0.031

GERP RS

4.1

Varity_R

0.54

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over