Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000253122.10(SLC6A8):c.87G>A(p.Gly29Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,080,808 control chromosomes in the GnomAD database, including 1 homozygotes. There are 180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G29G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 13 hem., cov: 20)

Exomes 𝑓: 0.00031 ( 1 hom. 167 hem. )

Consequence

SLC6A8
ENST00000253122.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.906

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 links:

PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

PNCK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant X-153688661-G-A is Benign according to our data. Variant chrX-153688661-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.906 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000222 (24/107987) while in subpopulation SAS AF = 0.00781 (20/2561). AF 95% confidence interval is 0.00518. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 13 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000253122.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.87G>A	p.Gly29Gly	synonymous	Exon 1 of 13	NP_005620.1
	SLC6A8	NM_001142805.2		c.87G>A	p.Gly29Gly	synonymous	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.87G>A	p.Gly29Gly	synonymous	Exon 1 of 13	ENSP00000253122.5
PNCK	ENST00000458354.5	TSL:3	c.-3+154C>T		intron	N/A	ENSP00000401542.1
PNCK	ENST00000480693.1	TSL:5	n.64+154C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000222

AC:

AN:

107973

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000995

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00777

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000195

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000982

AC:

AN:

61074

AF XY:

0.00214

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000312

AC:

304

AN:

972821

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

167

AN XY:

310985

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20012

American (AMR)

AF:

0.00

AC:

AN:

19082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15870

East Asian (EAS)

AF:

0.00

AC:

AN:

19999

South Asian (SAS)

AF:

0.00668

AC:

289

AN:

43262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2746

European-Non Finnish (NFE)

AF:

0.00000386

AC:

AN:

778007

Other (OTH)

AF:

0.000302

AC:

AN:

39701

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

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:

0.000222

AC:

AN:

107987

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

AN XY:

31393

show subpopulations

African (AFR)

AF:

0.0000993

AC:

AN:

30204

American (AMR)

AF:

0.00

AC:

AN:

10521

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2589

East Asian (EAS)

AF:

0.00

AC:

AN:

3277

South Asian (SAS)

AF:

0.00781

AC:

AN:

2561

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5179

Middle Eastern (MID)

AF:

0.00

AC:

AN:

202

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

51338

Other (OTH)

AF:

0.00

AC:

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

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:

0.0000264

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Creatine transporter deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

-0.91

PromoterAI

-0.039

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.7

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

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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

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over