chr5-1225449-T-C

Position:

• chr5-1225449-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A18	NM_182632.3	c.-29T>C		5_prime_UTR_variant	1/12	ENST00000324642.4	NP_872438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4	c.-29T>C		5_prime_UTR_variant	1/12	1	NM_182632.3	ENSP00000323549	P1
SLC6A18	ENST00000513607.2	n.41T>C		non_coding_transcript_exon_variant	1/3	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

GnomAD3 exomes AF: 0.754 AC: 165613 AN: 219550 Hom.: 63001 AF XY: 0.754 AC XY: 89754 AN XY: 119054

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 SAS exome AF: 0.745

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

Gnomad4 AFR exome AF: 0.799

Gnomad4 AMR exome AF: 0.754

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.749

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.758

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

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.764

Alfa AF: 0.777 Hom.: 12984

Bravo AF: 0.771

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.45

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: rs7728646; hg19: chr5-1225564;