NM_182632.3:c.301+17G>C

Variant names:

• chr5-1232376-G-C
• rs4975623
• NM_182632.3:c.301+17G>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.301+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 1,603,348 control chromosomes in the GnomAD database, including 659,199 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 0.91 (62837 hom., cov: 34)
  • Exomes 𝑓: 0.91 (596362 hom.)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 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.301+17G>C		intron	N/A	NP_872438.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A18	ENST00000324642.4	TSL:1 MANE Select	c.301+17G>C		intron	N/A	ENSP00000323549.3
	SLC6A18	ENST00000513607.2	TSL:3	n.370+17G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137814 AN: 152170 Hom.: 62788 Cov.: 34

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.913

GnomAD2 exomes AF: 0.878 AC: 205281 AN: 233924 AF XY: 0.879

Gnomad AFR exome AF: 0.945

Gnomad AMR exome AF: 0.833

Gnomad ASJ exome AF: 0.944

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.929

Gnomad NFE exome AF: 0.921

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.905 AC: 1313279 AN: 1451060 Hom.: 596362 Cov.: 58 AF XY: 0.903 AC XY: 650940 AN XY: 720588

African (AFR) AF: 0.947 AC: 31607 AN: 33360

American (AMR) AF: 0.836 AC: 36529 AN: 43696

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 24343 AN: 25830

East Asian (EAS) AF: 0.679 AC: 26745 AN: 39366

South Asian (SAS) AF: 0.832 AC: 69975 AN: 84148

European-Finnish (FIN) AF: 0.931 AC: 48196 AN: 51774

Middle Eastern (MID) AF: 0.914 AC: 4347 AN: 4758

European-Non Finnish (NFE) AF: 0.919 AC: 1017901 AN: 1108206

Other (OTH) AF: 0.895 AC: 53636 AN: 59922

GnomAD4 genome AF: 0.906 AC: 137927 AN: 152288 Hom.: 62837 Cov.: 34 AF XY: 0.901 AC XY: 67111 AN XY: 74456

African (AFR) AF: 0.943 AC: 39204 AN: 41564

American (AMR) AF: 0.842 AC: 12889 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3285 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3130 AN: 5168

South Asian (SAS) AF: 0.817 AC: 3934 AN: 4818

European-Finnish (FIN) AF: 0.929 AC: 9867 AN: 10618

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62669 AN: 68026

Other (OTH) AF: 0.914 AC: 1931 AN: 2112

Alfa AF: 0.923 Hom.: 6912

Bravo AF: 0.902

Asia WGS AF: 0.769 AC: 2677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.27
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs4975623; hg19: chr5-1232491;