dbSNP rs144208211: SLC6A18:p.Val74Ile (chr5-1232278-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_182632.3(SLC6A18):c.220G>A(p.Val74Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,612,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

SLC6A18
NM_182632.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.850

Publications

2 publications found

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]

SLC6A18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07397014).

BP6

Variant 5-1232278-G-A is Benign according to our data. Variant chr5-1232278-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3165432.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182632.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A18	NM_182632.3	MANE Select	c.220G>A	p.Val74Ile	missense	Exon 2 of 12	NP_872438.2	Q96N87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A18	ENST00000324642.4	TSL:1 MANE Select	c.220G>A	p.Val74Ile	missense	Exon 2 of 12	ENSP00000323549.3	Q96N87
	SLC6A18	ENST00000513607.2	TSL:3	n.289G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000117

AC:

AN:

247942

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.0000984

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000952

AC:

139

AN:

1460674

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

726592

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33466

American (AMR)

AF:

0.000291

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86052

European-Finnish (FIN)

AF:

0.0000378

AC:

AN:

52842

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

1111866

Other (OTH)

AF:

0.000282

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41574

American (AMR)

AF:

0.000261

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000258

Hom.:

Bravo

AF:

0.000314

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000990

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.1

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.054

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.82

M_CAP

Benign

0.025

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

PhyloP100

0.85

PrimateAI

Benign

0.21

PROVEAN

Benign

0.78

REVEL

Benign

0.13

Sift

Benign

0.34

Sift4G

Benign

0.35

Polyphen

0.0070

Vest4

0.24

MVP

0.65

MPC

0.13

ClinPred

0.020

GERP RS

1.5

Varity_R

0.027

gMVP

0.077

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over