rs187400676

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005629.4(SLC6A8):c.1141+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,205,279 control chromosomes in the GnomAD database, including 17 homozygotes. There are 758 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 0.0037 ( 3 hom., 164 hem., cov: 24)

Exomes 𝑓: 0.0018 ( 14 hom. 594 hem. )

Consequence

SLC6A8
NM_005629.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.95

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

creatine transporter deficiency
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

SLC6A8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-153693604-G-A is Benign according to our data. Variant chrX-153693604-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 381457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00374 (422/112828) while in subpopulation AMR AF = 0.031 (333/10738). AF 95% confidence interval is 0.0283. There are 3 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC6A8	NM_005629.4 link	c.1141+18G>A	intron_variant	Intron 7 of 12	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2 link	c.1111+18G>A	intron_variant	Intron 7 of 12		NP_001136277.1
SLC6A8	NM_001142806.1 link	c.796+18G>A	intron_variant	Intron 7 of 12		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10 link	c.1141+18G>A		intron_variant	Intron 7 of 12	1	NM_005629.4	ENSP00000253122.5

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

426

AN:

112775

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00644

Gnomad SAS

AF:

0.000362

Gnomad FIN

AF:

0.00529

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.00461

GnomAD2 exomes

AF:

0.00596

AC:

1088

AN:

182547

AF XY:

0.00476

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00484

Gnomad FIN exome

AF:

0.00675

Gnomad NFE exome

AF:

0.000382

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00184

AC:

2012

AN:

1092451

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

594

AN XY:

358591

show subpopulations

African (AFR)

AF:

0.000228

AC:

AN:

26275

American (AMR)

AF:

0.0324

AC:

1139

AN:

35190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19354

East Asian (EAS)

AF:

0.0111

AC:

335

AN:

30188

South Asian (SAS)

AF:

0.000574

AC:

AN:

53983

European-Finnish (FIN)

AF:

0.00633

AC:

256

AN:

40423

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3414

European-Non Finnish (NFE)

AF:

0.000184

AC:

154

AN:

837766

Other (OTH)

AF:

0.00198

AC:

AN:

45858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

188

282

376

470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00374

AC:

422

AN:

112828

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

164

AN XY:

34974

show subpopulations

African (AFR)

AF:

0.000321

AC:

AN:

31154

American (AMR)

AF:

0.0310

AC:

333

AN:

10738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00618

AC:

AN:

3560

South Asian (SAS)

AF:

0.000364

AC:

AN:

2751

European-Finnish (FIN)

AF:

0.00529

AC:

AN:

6233

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000300

AC:

AN:

53301

Other (OTH)

AF:

0.00455

AC:

AN:

1538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.00578

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Creatine transporter deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.15

(source)

DANN

Benign

0.70

PhyloP100

-2.0

PromoterAI

0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over