NM_182632.3:c.514G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_182632.3(SLC6A18):​c.514G>T​(p.Asp172Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC6A18
NM_182632.3 missense

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A18NM_182632.3 linkc.514G>T p.Asp172Tyr missense_variant Exon 4 of 12 ENST00000324642.4 NP_872438.2 Q96N87

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A18ENST00000324642.4 linkc.514G>T p.Asp172Tyr missense_variant Exon 4 of 12 1 NM_182632.3 ENSP00000323549.3 Q96N87

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461726
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Uncertain
0.36
D
MutationAssessor
Pathogenic
3.7
H
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0080
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.70
Loss of disorder (P = 0.0612);
MVP
0.82
MPC
0.76
ClinPred
0.97
D
GERP RS
5.2
Varity_R
0.73
gMVP
0.78

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.

Other links and lift over

dbSNP: rs144201527; hg19: chr5-1235670; API