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GeneBe

5-1235512-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_182632.3(SLC6A18):c.471C>T(p.Ala157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,998 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 17 hom., cov: 33)
Exomes 𝑓: 0.010 ( 99 hom. )

Consequence

SLC6A18
NM_182632.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73
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 -13 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=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-1235512-C-T is Benign according to our data. Variant chr5-1235512-C-T is described in ClinVar as [Benign]. Clinvar id is 779239.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=-1.73 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0104 (15222/1461668) while in subpopulation MID AF= 0.0186 (107/5768). AF 95% confidence interval is 0.0157. There are 99 homozygotes in gnomad4_exome. There are 7660 alleles in male gnomad4_exome subpopulation. Median coverage is 31. 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 17 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC6A18NM_182632.3 linkuse as main transcriptc.471C>T p.Ala157= synonymous_variant 4/12 ENST00000324642.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC6A18ENST00000324642.4 linkuse as main transcriptc.471C>T p.Ala157= synonymous_variant 4/121 NM_182632.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00822
AC:
1251
AN:
152212
Hom.:
17
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00393
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00870
Gnomad ASJ
AF:
0.0161
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00579
Gnomad FIN
AF:
0.00367
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0119
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00841
AC:
2109
AN:
250910
Hom.:
15
AF XY:
0.00867
AC XY:
1178
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.00376
Gnomad AMR exome
AF:
0.00515
Gnomad ASJ exome
AF:
0.0153
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00768
Gnomad FIN exome
AF:
0.00370
Gnomad NFE exome
AF:
0.0118
Gnomad OTH exome
AF:
0.00981
GnomAD4 exome
AF:
0.0104
AC:
15222
AN:
1461668
Hom.:
99
Cov.:
31
AF XY:
0.0105
AC XY:
7660
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.00296
Gnomad4 AMR exome
AF:
0.00525
Gnomad4 ASJ exome
AF:
0.0143
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00670
Gnomad4 FIN exome
AF:
0.00443
Gnomad4 NFE exome
AF:
0.0117
Gnomad4 OTH exome
AF:
0.00972
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00821
AC:
1250
AN:
152330
Hom.:
17
Cov.:
33
AF XY:
0.00784
AC XY:
584
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.00392
Gnomad4 AMR
AF:
0.00869
Gnomad4 ASJ
AF:
0.0161
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00559
Gnomad4 FIN
AF:
0.00367
Gnomad4 NFE
AF:
0.0119
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.0109
Hom.:
3
Bravo
AF:
0.00799
Asia WGS
AF:
0.00404
AC:
14
AN:
3478
EpiCase
AF:
0.0139
EpiControl
AF:
0.0122

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 testingInvitaeFeb 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
5.7
Dann
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs74919274; hg19: chr5-1235627; API