5-1236097-T-G

Position:

• chr5-1236097-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000324642.4(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 ENST00000324642.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A18	NM_182632.3	c.621+435T>G		intron_variant		ENST00000324642.4	NP_872438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4	c.621+435T>G		intron_variant		1	NM_182632.3	ENSP00000323549	P1

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.333

Alfa AF: 0.376 Hom.: 13876

Bravo AF: 0.342

Asia WGS AF: 0.335 AC: 1164 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.49

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: rs7445640; hg19: chr5-1236212;