NM_005629.4:c.1713C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005629.4(SLC6A8):c.1713C>T(p.Cys571Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,207,372 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 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 0.000062 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.00012 ( 0 hom. 45 hem. )

Consequence

SLC6A8
NM_005629.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.148

Publications

0 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-153694835-C-T is Benign according to our data. Variant chrX-153694835-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.148 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLC6A8	NM_005629.4 link	c.1713C>T	p.Cys571Cys	synonymous_variant	Exon 12 of 13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2 link	c.1683C>T	p.Cys561Cys	synonymous_variant	Exon 12 of 13		NP_001136277.1
SLC6A8	NM_001142806.1 link	c.1368C>T	p.Cys456Cys	synonymous_variant	Exon 12 of 13		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC6A8	ENST00000253122.10 link	c.1713C>T	p.Cys571Cys	synonymous_variant	Exon 12 of 13	1	NM_005629.4	ENSP00000253122.5
SLC6A8	ENST00000430077.6 link	c.1368C>T	p.Cys456Cys	synonymous_variant	Exon 12 of 13	2		ENSP00000403041.2
SLC6A8	ENST00000485324.1 link	n.2020C>T		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.0000619

AC:

AN:

113004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000926

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000558

Gnomad SAS

AF:

0.000710

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000210

AC:

AN:

176273

AF XY:

0.000225

show subpopulations

Gnomad AFR exome

AF:

0.0000797

Gnomad AMR exome

AF:

0.000259

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000816

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000643

Gnomad OTH exome

AF:

0.000683

GnomAD4 exome

AF:

0.000118

AC:

129

AN:

1094368

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

360656

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26339

American (AMR)

AF:

0.000114

AC:

AN:

35020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19349

East Asian (EAS)

AF:

0.000365

AC:

AN:

30168

South Asian (SAS)

AF:

0.000913

AC:

AN:

53696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3373

European-Non Finnish (NFE)

AF:

0.0000547

AC:

AN:

840545

Other (OTH)

AF:

0.000349

AC:

AN:

45908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000619

AC:

AN:

113004

Hom.:

Cov.:

AF XY:

0.0000569

AC XY:

AN XY:

35158

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31152

American (AMR)

AF:

0.0000926

AC:

AN:

10795

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.000558

AC:

AN:

3585

South Asian (SAS)

AF:

0.000710

AC:

AN:

2816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6273

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53277

Other (OTH)

AF:

0.00

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

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:

0.0000868

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 04, 2017

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Creatine transporter deficiency

Benign:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Feb 10, 2017

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Jan 11, 2021

GeneDx

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

-0.46

CADD

Benign

0.66

(source)

DANN

Benign

0.64

PhyloP100

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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