Genetic Variant SLC6A18:p.Tyr319* (chr5-1240642-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_182632.3(SLC6A18):c.957C>G(p.Tyr319*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,613,604 control chromosomes in the GnomAD database, including 122,126 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.36 ( 10194 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111932 hom. )

Consequence

SLC6A18
NM_182632.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.30

Publications

36 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A18	NM_182632.3 link	c.957C>G	p.Tyr319*	stop_gained	Exon 7 of 12	ENST00000324642.4	NP_872438.2	Q96N87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4 link	c.957C>G	p.Tyr319*	stop_gained	Exon 7 of 12	1	NM_182632.3	ENSP00000323549.3		Q96N87

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55092

AN:

151906

Hom.:

10193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.335

GnomAD2 exomes

AF:

0.362

AC:

90904

AN:

251186

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.351

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.385

Gnomad OTH exome

AF:

0.348

GnomAD4 exome

AF:

0.389

AC:

569177

AN:

1461580

Hom.:

111932

Cov.:

AF XY:

0.389

AC XY:

282689

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.351

AC:

11735

AN:

33480

American (AMR)

AF:

0.375

AC:

16774

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

7544

AN:

26130

East Asian (EAS)

AF:

0.330

AC:

13092

AN:

39696

South Asian (SAS)

AF:

0.396

AC:

34127

AN:

86254

European-Finnish (FIN)

AF:

0.328

AC:

17468

AN:

53262

Middle Eastern (MID)

AF:

0.312

AC:

1800

AN:

5768

European-Non Finnish (NFE)

AF:

0.400

AC:

444638

AN:

1111892

Other (OTH)

AF:

0.364

AC:

21999

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

19627

39254

58881

78508

98135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13926

27852

41778

55704

69630

<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:

0.363

AC:

55114

AN:

152024

Hom.:

10194

Cov.:

AF XY:

0.359

AC XY:

26665

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.346

AC:

14328

AN:

41438

American (AMR)

AF:

0.376

AC:

5745

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1004

AN:

3468

East Asian (EAS)

AF:

0.245

AC:

1265

AN:

5158

South Asian (SAS)

AF:

0.395

AC:

1898

AN:

4808

European-Finnish (FIN)

AF:

0.323

AC:

3412

AN:

10578

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26339

AN:

67974

Other (OTH)

AF:

0.332

AC:

700

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1777

3553

5330

7106

8883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.331

Hom.:

2775

Bravo

AF:

0.363

TwinsUK

AF:

0.407

AC:

1508

ALSPAC

AF:

0.395

AC:

1521

ESP6500AA

AF:

0.348

AC:

1534

ESP6500EA

AF:

0.373

AC:

3206

ExAC

AF:

0.364

AC:

44213

Asia WGS

AF:

0.331

AC:

1151

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.78

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.051

PhyloP100

-3.3

Vest4

0.25

GERP RS

-3.1

Mutation Taster

=145/55

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over