rs7447815

Positions:

• chr5-1240642-C-G
• chr5-1240642-C-T

Variant summary

Our verdict is Benign. Variant got -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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC6A18	NM_182632.3	c.957C>G	p.Tyr319*	stop_gained	7/12	ENST00000324642.4	NP_872438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4	c.957C>G	p.Tyr319*	stop_gained	7/12	1	NM_182632.3	ENSP00000323549.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55092 AN: 151906 Hom.: 10193 Cov.: 32

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

GnomAD3 exomes AF: 0.362 AC: 90904 AN: 251186 Hom.: 16857 AF XY: 0.364 AC XY: 49499 AN XY: 135802

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 SAS exome AF: 0.400

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.: 50 AF XY: 0.389 AC XY: 282689 AN XY: 727094

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.363 AC: 55114 AN: 152024 Hom.: 10194 Cov.: 32 AF XY: 0.359 AC XY: 26665 AN XY: 74328

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.332

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	T
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Benign	0.95
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.051	N
Vest4		0.25
GERP RS		-3.1

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

LitVar

Other links and lift over

dbSNP: rs7447815; hg19: chr5-1240757; COSMIC: COSV57250173;