NM_182632.3:c.621+435T>G

Variant names:

• chr5-1236097-T-G
• rs7445640
• NM_182632.3:c.621+435T>G

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+435T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,990 control chromosomes in the GnomAD database, including 9,484 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 0.34 (9484 hom., cov: 32)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 11 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 (SAS) allele frequency at 95% confidence interval = 0.425 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A18	NM_182632.3	MANE Select	c.621+435T>G		intron	N/A	NP_872438.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A18	ENST00000324642.4	TSL:1 MANE Select	c.621+435T>G		intron	N/A	ENSP00000323549.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52317 AN: 151872 Hom.: 9480 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.344 AC: 52335 AN: 151990 Hom.: 9484 Cov.: 32 AF XY: 0.342 AC XY: 25376 AN XY: 74292

African (AFR) AF: 0.254 AC: 10541 AN: 41490

American (AMR) AF: 0.374 AC: 5714 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1213 AN: 5156

South Asian (SAS) AF: 0.441 AC: 2123 AN: 4816

European-Finnish (FIN) AF: 0.322 AC: 3391 AN: 10524

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27148 AN: 67942

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.378 Hom.: 19213

Bravo AF: 0.342

Asia WGS AF: 0.335 AC: 1164 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.49
PhyloP100		-0.64
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: rs7445640; hg19: chr5-1236212;