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GeneBe

5-1238000-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_182632.3(SLC6A18):c.672C>T(p.Leu224=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,206 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 25 hom. )

Consequence

SLC6A18
NM_182632.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33
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 Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-1238000-C-T is Benign according to our data. Variant chr5-1238000-C-T is described in ClinVar as [Benign]. Clinvar id is 715978.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.33 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1535/152368) while in subpopulation AFR AF= 0.0353 (1468/41574). AF 95% confidence interval is 0.0338. There are 26 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC6A18NM_182632.3 linkuse as main transcriptc.672C>T p.Leu224= synonymous_variant 5/12 ENST00000324642.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC6A18ENST00000324642.4 linkuse as main transcriptc.672C>T p.Leu224= synonymous_variant 5/121 NM_182632.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1535
AN:
152250
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0354
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00265
AC:
666
AN:
251474
Hom.:
6
AF XY:
0.00193
AC XY:
262
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.0369
Gnomad AMR exome
AF:
0.00153
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:
0.0000703
Gnomad OTH exome
AF:
0.000977
GnomAD4 exome
AF:
0.00106
AC:
1544
AN:
1461838
Hom.:
25
Cov.:
30
AF XY:
0.000880
AC XY:
640
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0378
Gnomad4 AMR exome
AF:
0.00170
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:
0.0000621
Gnomad4 OTH exome
AF:
0.00217
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1535
AN:
152368
Hom.:
26
Cov.:
32
AF XY:
0.00966
AC XY:
720
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0353
Gnomad4 AMR
AF:
0.00248
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00429
Hom.:
7
Bravo
AF:
0.0114
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

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 submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
0.67
Dann
Benign
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs111842636; hg19: chr5-1238115; API