5-1232766-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182632.3(SLC6A18):​c.317C>T​(p.Thr106Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

SLC6A18
NM_182632.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10487798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A18NM_182632.3 linkc.317C>T p.Thr106Met missense_variant Exon 3 of 12 ENST00000324642.4 NP_872438.2 Q96N87

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A18ENST00000324642.4 linkc.317C>T p.Thr106Met missense_variant Exon 3 of 12 1 NM_182632.3 ENSP00000323549.3 Q96N87
SLC6A18ENST00000513607.2 linkn.386C>T non_coding_transcript_exon_variant Exon 3 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250372
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135386
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000708
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000445
AC:
65
AN:
1460764
Hom.:
0
Cov.:
31
AF XY:
0.0000427
AC XY:
31
AN XY:
726634
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152298
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.317C>T (p.T106M) alteration is located in exon 3 (coding exon 3) of the SLC6A18 gene. This alteration results from a C to T substitution at nucleotide position 317, causing the threonine (T) at amino acid position 106 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
9.0
DANN
Benign
0.90
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.090
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.38
N
REVEL
Benign
0.056
Sift
Benign
0.045
D
Sift4G
Benign
0.097
T
Polyphen
0.38
B
Vest4
0.29
MutPred
0.44
Loss of catalytic residue at T106 (P = 0.0247);
MVP
0.52
MPC
0.22
ClinPred
0.035
T
GERP RS
1.4
Varity_R
0.017
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs757737380; hg19: chr5-1232881; API