Genetic Variant NM_005629.4:c.1768-8_1768-7dupTC (chrX-153695062-C-CCT) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005629.4(SLC6A8):c.1768-8_1768-7dupTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 1,196,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000069 ( 0 hom. 24 hem. )

Consequence

SLC6A8
NM_005629.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00700

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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant X-153695062-C-CCT is Benign according to our data. Variant chrX-153695062-C-CCT is described in ClinVar as Likely_benign. ClinVar VariationId is 1583949.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 24 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC6A8	NM_005629.4	MANE Select	c.1768-8_1768-7dupTC	splice_region intron	N/A	NP_005620.1
SLC6A8	NM_001142805.2		c.1738-8_1738-7dupTC	splice_region intron	N/A	NP_001136277.1
SLC6A8	NM_001142806.1		c.1423-8_1423-7dupTC	splice_region intron	N/A	NP_001136278.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.1768-12_1768-11insCT	intron	N/A	ENSP00000253122.5
SLC6A8	ENST00000430077.6	TSL:2	c.1423-12_1423-11insCT	intron	N/A	ENSP00000403041.2
SLC6A8	ENST00000485324.1	TSL:2	n.2075-12_2075-11insCT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000355

AC:

AN:

112688

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000751

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000192

AC:

AN:

156096

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000451

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000692

AC:

AN:

1083975

Hom.:

Cov.:

AF XY:

0.0000679

AC XY:

AN XY:

353255

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26147

American (AMR)

AF:

0.00

AC:

AN:

34010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19027

East Asian (EAS)

AF:

0.00

AC:

AN:

29642

South Asian (SAS)

AF:

0.00

AC:

AN:

52082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39269

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3742

European-Non Finnish (NFE)

AF:

0.0000839

AC:

AN:

834594

Other (OTH)

AF:

0.000110

AC:

AN:

45462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000355

AC:

AN:

112688

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

34846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30977

American (AMR)

AF:

0.00

AC:

AN:

10765

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00

AC:

AN:

3581

South Asian (SAS)

AF:

0.00

AC:

AN:

2749

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6285

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000751

AC:

AN:

53242

Other (OTH)

AF:

0.00

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Creatine transporter deficiency

Benign:1

Aug 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.0070

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over