rs200695210

Positions:

chrX-153694528-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005629.4(SLC6A8):c.1496-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,205,694 control chromosomes in the GnomAD database, including 4 homozygotes. There are 332 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., 134 hem., cov: 23)

Exomes 𝑓: 0.00064 ( 0 hom. 198 hem. )

Consequence

SLC6A8
NM_005629.4 splice_region, intron

Scores

Splicing: ADA: 0.00004396

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.414

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:

SLC6A8 (HGNC:):

SLC6A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-153694528-C-T is Benign according to our data. Variant chrX-153694528-C-T is described in ClinVar as [Benign]. Clinvar id is 383235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153694528-C-T is described in Lovd as [Likely_benign]. Variant chrX-153694528-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00449 (499/111068) while in subpopulation AFR AF= 0.0155 (473/30490). AF 95% confidence interval is 0.0144. There are 4 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLC6A8	NM_005629.4 linkuse as main transcript	c.1496-5C>T	splice_region_variant, intron_variant	ENST00000253122.10	NP_005620.1	P48029-1X5D9C4
SLC6A8	NM_001142805.2 linkuse as main transcript	c.1466-5C>T	splice_region_variant, intron_variant		NP_001136277.1	P48029Q59EV7
SLC6A8	NM_001142806.1 linkuse as main transcript	c.1151-5C>T	splice_region_variant, intron_variant		NP_001136278.1	P48029-4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.1496-5C>T	splice_region_variant, intron_variant		1	NM_005629.4	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000430077.6 linkuse as main transcript	c.1151-5C>T	splice_region_variant, intron_variant		2		ENSP00000403041.2	P48029-4
SLC6A8	ENST00000413787.1 linkuse as main transcript	c.425-5C>T	splice_region_variant, intron_variant		5		ENSP00000400463.1	H7C1I2
SLC6A8	ENST00000485324.1 linkuse as main transcript	n.1798C>T	non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

499

AN:

111016

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

134

AN XY:

33218

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000758

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:

0.000246

Gnomad OTH

AF:

0.00333

GnomAD3 exomes

AF:

0.00145

AC:

265

AN:

182957

Hom.:

AF XY:

0.000915

AC XY:

AN XY:

67753

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.000884

GnomAD4 exome

AF:

0.000642

AC:

703

AN:

1094626

Hom.:

Cov.:

AF XY:

0.000549

AC XY:

198

AN XY:

360344

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.000909

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.000166

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.000783

GnomAD4 genome

AF:

0.00449

AC:

499

AN:

111068

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

134

AN XY:

33282

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.000757

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000246

Gnomad4 OTH

AF:

0.00329

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00499

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 08, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Creatine transporter deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2017

This alteration is classified as 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

-0.85

CADD

Benign

1.3

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.046

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over