NM_005629.4:c.1626C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005629.4(SLC6A8):c.1626C>T(p.Tyr542Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,209,756 control chromosomes in the GnomAD database, including 1 homozygotes. There are 57 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 0.00040 ( 0 hom., 8 hem., cov: 25)

Exomes 𝑓: 0.00016 ( 1 hom. 49 hem. )

Consequence

SLC6A8
NM_005629.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0440

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant X-153694748-C-T is Benign according to our data. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694748-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 416001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.044 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4 link	c.1626C>T	p.Tyr542Tyr	synonymous_variant	Exon 12 of 13	ENST00000253122.10	NP_005620.1	P48029-1X5D9C4
SLC6A8	NM_001142805.2 link	c.1596C>T	p.Tyr532Tyr	synonymous_variant	Exon 12 of 13		NP_001136277.1	P48029Q59EV7
SLC6A8	NM_001142806.1 link	c.1281C>T	p.Tyr427Tyr	synonymous_variant	Exon 12 of 13		NP_001136278.1	P48029-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A8	ENST00000253122.10 link	c.1626C>T	p.Tyr542Tyr	synonymous_variant	Exon 12 of 13	1	NM_005629.4	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000430077.6 link	c.1281C>T	p.Tyr427Tyr	synonymous_variant	Exon 12 of 13	2		ENSP00000403041.2	P48029-4
SLC6A8	ENST00000485324.1 link	n.1933C>T		non_coding_transcript_exon_variant	Exon 5 of 6	2
SLC6A8	ENST00000413787.1 link	c.*172C>T		downstream_gene_variant		5		ENSP00000400463.1	H7C1I2

Frequencies

GnomAD3 genomes

AF:

0.000400

AC:

AN:

112553

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000208

AC:

AN:

182414

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.000919

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000313

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000157

AC:

172

AN:

1097153

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

362897

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

26367

American (AMR)

AF:

0.0000284

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.000232

AC:

AN:

30205

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54099

European-Finnish (FIN)

AF:

0.000248

AC:

AN:

40368

Middle Eastern (MID)

AF:

0.000274

AC:

AN:

3646

European-Non Finnish (NFE)

AF:

0.000138

AC:

116

AN:

841874

Other (OTH)

AF:

0.000217

AC:

AN:

46021

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000400

AC:

AN:

112603

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

34777

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

31094

American (AMR)

AF:

0.00

AC:

AN:

10741

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.000281

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2754

European-Finnish (FIN)

AF:

0.000161

AC:

AN:

6197

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

53169

Other (OTH)

AF:

0.00

AC:

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000582

Hom.:

Bravo

AF:

0.000412

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 13, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC6A8: BP4, BP7 -

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

- -

Creatine deficiency syndrome 1

Benign:1

Dec 06, 2019

Natera, Inc.

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.088

(source)

DANN

Benign

0.36

PhyloP100

-0.044

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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