5-1225449-T-C

Variant names:

• chr5-1225449-T-C
• rs7728646
• NM_182632.3:c.-29T>C

Variant summary

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

The NM_182632.3(SLC6A18):​c.-29T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,591,902 control chromosomes in the GnomAD database, including 479,117 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 0.78 (45921 hom., cov: 34)
  • Exomes 𝑓: 0.77 (433196 hom.)
• Consequence: SLC6A18 NM_182632.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.89
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 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.-29T>C		5_prime_UTR	Exon 1 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.-29T>C		5_prime_UTR	Exon 1 of 12	ENSP00000323549.3	Q96N87
	SLC6A18	ENST00000513607.2	TSL:3	n.41T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117858 AN: 151964 Hom.: 45880 Cov.: 34

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.762

GnomAD2 exomes AF: 0.754 AC: 165613 AN: 219550 AF XY: 0.754

Gnomad AFR exome AF: 0.791

Gnomad AMR exome AF: 0.755

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.569

Gnomad FIN exome AF: 0.833

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.759

GnomAD4 exome AF: 0.774 AC: 1114834 AN: 1439820 Hom.: 433196 Cov.: 41 AF XY: 0.773 AC XY: 552713 AN XY: 715082

African (AFR) AF: 0.799 AC: 26250 AN: 32842

American (AMR) AF: 0.754 AC: 31808 AN: 42166

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 18269 AN: 25612

East Asian (EAS) AF: 0.616 AC: 23909 AN: 38838

South Asian (SAS) AF: 0.749 AC: 62941 AN: 84012

European-Finnish (FIN) AF: 0.823 AC: 41675 AN: 50614

Middle Eastern (MID) AF: 0.741 AC: 3199 AN: 4316

European-Non Finnish (NFE) AF: 0.782 AC: 861735 AN: 1102004

Other (OTH) AF: 0.758 AC: 45048 AN: 59416

GnomAD4 genome AF: 0.776 AC: 117961 AN: 152082 Hom.: 45921 Cov.: 34 AF XY: 0.774 AC XY: 57580 AN XY: 74378

African (AFR) AF: 0.796 AC: 33025 AN: 41472

American (AMR) AF: 0.735 AC: 11234 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2473 AN: 3470

East Asian (EAS) AF: 0.573 AC: 2962 AN: 5166

South Asian (SAS) AF: 0.743 AC: 3577 AN: 4814

European-Finnish (FIN) AF: 0.834 AC: 8837 AN: 10596

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53273 AN: 67962

Other (OTH) AF: 0.764 AC: 1613 AN: 2112

Alfa AF: 0.777 Hom.: 13241

Bravo AF: 0.771

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.45
PhyloP100		-4.9
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	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: rs7728646; hg19: chr5-1225564;