Variant chr5-1235512-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_182632.3(SLC6A18):c.471C>T(p.Ala157Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,998 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 17 hom., cov: 33)

Exomes 𝑓: 0.010 ( 99 hom. )

Consequence

SLC6A18
NM_182632.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.73

Variant links:

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]

SLC6A18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 5-1235512-C-T is Benign according to our data. Variant chr5-1235512-C-T is described in ClinVar as [Benign]. Clinvar id is 779239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0104 (15222/1461668) while in subpopulation MID AF= 0.0186 (107/5768). AF 95% confidence interval is 0.0157. There are 99 homozygotes in gnomad4_exome. There are 7660 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A18	NM_182632.3 linkuse as main transcript	c.471C>T	p.Ala157Ala	synonymous_variant	4/12	ENST00000324642.4	NP_872438.2	Q96N87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4 linkuse as main transcript	c.471C>T	p.Ala157Ala	synonymous_variant	4/12	1	NM_182632.3	ENSP00000323549.3		Q96N87

Frequencies

GnomAD3 genomes

AF:

0.00822

AC:

1251

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00841

AC:

2109

AN:

250910

Hom.:

AF XY:

0.00867

AC XY:

1178

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.00376

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00768

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00981

GnomAD4 exome

AF:

0.0104

AC:

15222

AN:

1461668

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

7660

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.00525

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00670

Gnomad4 FIN exome

AF:

0.00443

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00972

GnomAD4 genome

AF:

0.00821

AC:

1250

AN:

152330

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

584

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00392

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00799

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0139

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.7

DANN

Benign

0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over