rs149753564

Variant summary

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

The NM_182632.3(SLC6A18):ā€‹c.127C>Gā€‹(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: š‘“ 0.00091 ( 0 hom., cov: 35)
Exomes š‘“: 0.00073 ( 6 hom. )

Consequence

SLC6A18
NM_182632.3 missense

Scores

6
7
6

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]

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
SLC6A18NM_182632.3 linkc.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
SLC6A18ENST00000324642.4 linkc.127C>G p.Arg43Gly missense_variant Exon 1 of 12 1 NM_182632.3 ENSP00000323549.3 Q96N87
SLC6A18ENST00000513607.2 linkn.196C>G non_coding_transcript_exon_variant Exon 1 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.000906
AC:
138
AN:
152234
Hom.:
0
Cov.:
35
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.:
1
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.:
6
Cov.:
35
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.:
0
Cov.:
35
AF XY:
0.00111
AC XY:
83
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.:
0
Bravo
AF:
0.000351
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000930
AC:
8
ExAC
AF:
0.00130
AC:
158
Asia WGS
AF:
0.00779
AC:
27
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
T
BayesDel_noAF
Pathogenic
0.29
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.52
D
Eigen
Benign
0.068
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.68
D
LIST_S2
Pathogenic
1.0
D
M_CAP
Uncertain
0.26
D
MetaRNN
Benign
0.11
T
MetaSVM
Uncertain
0.72
D
MutationAssessor
Pathogenic
4.5
H
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-6.5
D
REVEL
Pathogenic
0.71
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.89
MVP
0.80
MPC
0.78
ClinPred
0.24
T
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.

Other links and lift over

dbSNP: rs149753564; hg19: chr5-1225719; API