rs148232368

Positions:

chrX-153693043-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_005629.4(SLC6A8):c.780C>T(p.Ile260Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,209,720 control chromosomes in the GnomAD database, including 1 homozygotes. There are 118 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., 53 hem., cov: 25)

Exomes 𝑓: 0.00019 ( 0 hom. 65 hem. )

Consequence

SLC6A8
NM_005629.4 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.959

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant X-153693043-C-T is Benign according to our data. Variant chrX-153693043-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 383165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153693043-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.959 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00168 (190/112892) while in subpopulation AFR AF= 0.00584 (182/31163). AF 95% confidence interval is 0.00515. There are 1 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 53 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A8	NM_005629.4 linkuse as main transcript	c.780C>T	p.Ile260Ile	splice_region_variant, synonymous_variant	5/13	ENST00000253122.10	NP_005620.1	P48029-1X5D9C4
SLC6A8	NM_001142805.2 linkuse as main transcript	c.780C>T	p.Ile260Ile	splice_region_variant, synonymous_variant	5/13		NP_001136277.1	P48029Q59EV7
SLC6A8	NM_001142806.1 linkuse as main transcript	c.435C>T	p.Ile145Ile	splice_region_variant, synonymous_variant	5/13		NP_001136278.1	P48029-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.780C>T	p.Ile260Ile	splice_region_variant, synonymous_variant	5/13	1	NM_005629.4	ENSP00000253122.5		P48029-1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

190

AN:

112838

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

AN XY:

35008

show subpopulations

Gnomad AFR

AF:

0.00585

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000464

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:

0.00

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.000428

AC:

AN:

182298

Hom.:

AF XY:

0.000401

AC XY:

AN XY:

67384

show subpopulations

Gnomad AFR exome

AF:

0.00482

Gnomad AMR exome

AF:

0.000438

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

AF:

0.000190

AC:

208

AN:

1096828

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

362786

show subpopulations

Gnomad4 AFR exome

AF:

0.00565

Gnomad4 AMR exome

AF:

0.000511

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.00168

AC:

190

AN:

112892

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

AN XY:

35072

show subpopulations

Gnomad4 AFR

AF:

0.00584

Gnomad4 AMR

AF:

0.000463

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00196

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00200

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 20, 2018	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, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 12, 2024	- -

Creatine transporter deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

SLC6A8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2024

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

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 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

-0.34

CADD

Benign

8.7

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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