rs6554677

Variant names:

• chr5-1236176-G-A
• rs6554677
• NM_182632.3:c.621+514G>A

Variant summary

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

The NM_182632.3(SLC6A18):​c.621+514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,750 control chromosomes in the GnomAD database, including 1,488 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.

• Frequency: Genomes: 𝑓 0.12 (1488 hom., cov: 32)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 5 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A18	NM_182632.3	c.621+514G>A		intron_variant	Intron 4 of 11	ENST00000324642.4	NP_872438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4	c.621+514G>A		intron_variant	Intron 4 of 11	1	NM_182632.3	ENSP00000323549.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17864 AN: 151634 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0888

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.118 AC: 17892 AN: 151750 Hom.: 1488 Cov.: 32 AF XY: 0.118 AC XY: 8754 AN XY: 74144

African (AFR) AF: 0.234 AC: 9666 AN: 41334

American (AMR) AF: 0.0816 AC: 1246 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3470

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5156

South Asian (SAS) AF: 0.0570 AC: 273 AN: 4788

European-Finnish (FIN) AF: 0.131 AC: 1376 AN: 10474

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4812 AN: 67954

Other (OTH) AF: 0.0878 AC: 185 AN: 2106

Alfa AF: 0.0970 Hom.: 610

Bravo AF: 0.122

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.39
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6554677; hg19: chr5-1236291;