rs138064933

Positions:

chrX-153693076-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005629.4(SLC6A8):c.813C>T(p.Val271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,209,832 control chromosomes in the GnomAD database, including 13 homozygotes. There are 1,348 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., 80 hem., cov: 24)

Exomes 𝑓: 0.0034 ( 11 hom. 1268 hem. )

Consequence

SLC6A8
NM_005629.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.488

Variant links:

Genes affected

SLC6A8 (HGNC:11055): (solute carrier family 6 member 8) The protein encoded by this gene is a plasma membrane protein whose function is to transport creatine into and out of cells. Defects in this gene can result in X-linked creatine deficiency syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

SLC6A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050970614).

BP6

Variant X-153693076-C-T is Benign according to our data. Variant chrX-153693076-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 379427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153693076-C-T is described in Lovd as [Likely_benign]. Variant chrX-153693076-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.488 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC6A8	NM_005629.4 linkuse as main transcript	c.813C>T	p.Val271=	synonymous_variant	5/13	ENST00000253122.10
SLC6A8	NM_001142805.2 linkuse as main transcript	c.813C>T	p.Val271=	synonymous_variant	5/13
SLC6A8	NM_001142806.1 linkuse as main transcript	c.468C>T	p.Val156=	synonymous_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.813C>T	p.Val271=	synonymous_variant	5/13	1	NM_005629.4	P1	P48029-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

282

AN:

112803

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

AN XY:

34951

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00158

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00252

Gnomad FIN

AF:

0.000958

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.00396

GnomAD3 exomes

AF:

0.00336

AC:

613

AN:

182324

Hom.:

AF XY:

0.00347

AC XY:

234

AN XY:

67342

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.000986

Gnomad ASJ exome

AF:

0.0345

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00237

Gnomad FIN exome

AF:

0.000818

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.00400

GnomAD4 exome

AF:

0.00338

AC:

3705

AN:

1096974

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

1268

AN XY:

362736

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000994

Gnomad4 ASJ exome

AF:

0.0361

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00263

Gnomad4 FIN exome

AF:

0.000840

Gnomad4 NFE exome

AF:

0.00307

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00248

AC:

280

AN:

112858

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

AN XY:

35016

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00158

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00253

Gnomad4 FIN

AF:

0.000958

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00390

Alfa

AF:

0.00651

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00431

AC:

ExAC

AF:

0.00330

AC:

400

EpiCase

AF:

0.00425

EpiControl

AF:

0.00339

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 22, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 2021	This variant is associated with the following publications: (PMID: 16738945) -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Creatine transporter deficiency

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 17, 2019

- -

SLC6A8-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.96

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0051

MetaSVM

Uncertain

-0.21

MutationTaster

Benign

1.0

D;D

PROVEAN

Benign

1.7

REVEL

Benign

0.19

Sift

Pathogenic

0.0

MVP

0.69

ClinPred

0.056

GERP RS

4.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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