dbSNP rs782234529: SLC6A8:c.1768-9C>G (chrX-153695065-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005629.4(SLC6A8):c.1768-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,197,991 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000044 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )

Consequence

SLC6A8
NM_005629.4 intron

Scores

Splicing: ADA: 0.0003980

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.159

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-153695065-C-G is Benign according to our data. Variant chrX-153695065-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 533707.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4 link	c.1768-9C>G	intron_variant	Intron 12 of 12	ENST00000253122.10	NP_005620.1	P48029-1X5D9C4
SLC6A8	NM_001142805.2 link	c.1738-9C>G	intron_variant	Intron 12 of 12		NP_001136277.1	P48029Q59EV7
SLC6A8	NM_001142806.1 link	c.1423-9C>G	intron_variant	Intron 12 of 12		NP_001136278.1	P48029-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A8	ENST00000253122.10 link	c.1768-9C>G	intron_variant	Intron 12 of 12	1	NM_005629.4	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000430077.6 link	c.1423-9C>G	intron_variant	Intron 12 of 12	2		ENSP00000403041.2	P48029-4
SLC6A8	ENST00000485324.1 link	n.2075-9C>G	intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000444

AC:

AN:

112699

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000635

AC:

AN:

157438

AF XY:

0.0000818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000798

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1085240

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

354034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26165

American (AMR)

AF:

0.00

AC:

AN:

34089

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19072

East Asian (EAS)

AF:

0.000337

AC:

AN:

29710

South Asian (SAS)

AF:

0.00

AC:

AN:

52152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39333

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3760

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

835441

Other (OTH)

AF:

0.0000220

AC:

AN:

45518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.0000443

AC:

AN:

112751

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

34911

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31068

American (AMR)

AF:

0.00

AC:

AN:

10775

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00140

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2747

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53226

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Creatine transporter deficiency

Benign:1

Oct 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SLC6A8-related disorder

Benign:1

Jul 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.5

(source)

DANN

Benign

0.67

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00040

dbscSNV1_RF

Benign

0.034

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

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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