rs4073918

Variant names:

• chr5-1244310-C-T
• rs4073918
• NM_182632.3:c.1433C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182632.3(SLC6A18):​c.1433C>T​(p.Pro478Leu) variant causes a missense change. The variant allele was found at a frequency of 0.755 in 1,613,792 control chromosomes in the GnomAD database, including 466,262 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45815 hom., cov: 31)
  • Exomes 𝑓: 0.75 (420447 hom.)
• Consequence: SLC6A18 NM_182632.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42
• Publications: 45 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8419563E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

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.1433C>T	p.Pro478Leu	missense	Exon 10 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.1433C>T	p.Pro478Leu	missense	Exon 10 of 12	ENSP00000323549.3	Q96N87

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116632 AN: 151910 Hom.: 45771 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.710 AC: 178535 AN: 251440 AF XY: 0.712

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.727

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.714

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.731

GnomAD4 exome AF: 0.754 AC: 1102313 AN: 1461764 Hom.: 420447 Cov.: 63 AF XY: 0.753 AC XY: 547232 AN XY: 727180

African (AFR) AF: 0.881 AC: 29507 AN: 33480

American (AMR) AF: 0.687 AC: 30739 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 18973 AN: 26132

East Asian (EAS) AF: 0.367 AC: 14569 AN: 39700

South Asian (SAS) AF: 0.696 AC: 60068 AN: 86254

European-Finnish (FIN) AF: 0.719 AC: 38382 AN: 53404

Middle Eastern (MID) AF: 0.769 AC: 4436 AN: 5766

European-Non Finnish (NFE) AF: 0.774 AC: 861003 AN: 1111920

Other (OTH) AF: 0.739 AC: 44636 AN: 60388

GnomAD4 genome AF: 0.768 AC: 116727 AN: 152028 Hom.: 45815 Cov.: 31 AF XY: 0.758 AC XY: 56341 AN XY: 74294

African (AFR) AF: 0.871 AC: 36134 AN: 41480

American (AMR) AF: 0.714 AC: 10897 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2517 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1426 AN: 5130

South Asian (SAS) AF: 0.688 AC: 3318 AN: 4822

European-Finnish (FIN) AF: 0.714 AC: 7555 AN: 10578

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52380 AN: 67964

Other (OTH) AF: 0.748 AC: 1582 AN: 2116

Alfa AF: 0.764 Hom.: 190020

Bravo AF: 0.772

TwinsUK AF: 0.767 AC: 2843

ALSPAC AF: 0.775 AC: 2987

ESP6500AA AF: 0.863 AC: 3803

ESP6500EA AF: 0.764 AC: 6571

ExAC AF: 0.717 AC: 87057

Asia WGS AF: 0.520 AC: 1813 AN: 3478

EpiCase AF: 0.773

EpiControl AF: 0.765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.5	N
PhyloP100		5.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	4.9	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.030
MPC		0.16
ClinPred		0.020	T
GERP RS		4.9
Varity_R		0.041
gMVP		0.19
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4073918; hg19: chr5-1244425; COSMIC: COSV57251360;