dbSNP rs149753564: SLC6A18:p.Arg43Gly (chr5-1225604-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_182632.3(SLC6A18):c.127C>G(p.Arg43Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 1,604,440 control chromosomes in the GnomAD database, including 6 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 0.00091 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00073 ( 6 hom. )

Consequence

SLC6A18
NM_182632.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.149

Variant links:

Genes affected

SLC6A18 (HGNC:26441): (solute carrier family 6 member 18) The SLC6 family of proteins, which includes SLC6A18, act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine. SLC6 proteins are sodium cotransporters that derive the energy for solute transport from the electrochemical gradient for sodium ions (Hoglund et al., 2005 [PubMed 16125675]).[supplied by OMIM, Apr 2010]

SLC6A18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11447504).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A18	NM_182632.3 link	c.127C>G	p.Arg43Gly	missense_variant	Exon 1 of 12	ENST00000324642.4	NP_872438.2	Q96N87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4 link	c.127C>G	p.Arg43Gly	missense_variant	Exon 1 of 12	1	NM_182632.3	ENSP00000323549.3		Q96N87
SLC6A18	ENST00000513607.2 link	n.196C>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.000906

AC:

138

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00113

AC:

271

AN:

239258

Hom.:

AF XY:

0.00112

AC XY:

145

AN XY:

128970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000328

Gnomad EAS exome

AF:

0.00122

Gnomad SAS exome

AF:

0.000248

Gnomad FIN exome

AF:

0.00629

Gnomad NFE exome

AF:

0.000941

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.000727

AC:

1056

AN:

1452088

Hom.:

Cov.:

AF XY:

0.000722

AC XY:

521

AN XY:

721758

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000395

Gnomad4 EAS exome

AF:

0.00187

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.00622

Gnomad4 NFE exome

AF:

0.000522

Gnomad4 OTH exome

AF:

0.000767

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152352

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000611

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00130

AC:

158

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Pathogenic

0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.068

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.68

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.72

MutationAssessor

Pathogenic

4.5

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.5

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.89

MVP

0.80

MPC

0.78

ClinPred

0.24

GERP RS

-5.1

Varity_R

0.92

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over