rs782589547

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005629.4(SLC6A8):c.1496-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,205,776 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 76 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00020 ( 0 hom. 74 hem. )

Consequence

SLC6A8
NM_005629.4 splice_region, intron

Scores

Splicing: ADA: 0.00007542

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.71

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-153694529-G-A is Benign according to our data. Variant chrX-153694529-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLC6A8	NM_005629.4 linkuse as main transcript	c.1496-4G>A	splice_region_variant, intron_variant	ENST00000253122.10	NP_005620.1	P48029-1X5D9C4
SLC6A8	NM_001142805.2 linkuse as main transcript	c.1466-4G>A	splice_region_variant, intron_variant		NP_001136277.1	P48029Q59EV7
SLC6A8	NM_001142806.1 linkuse as main transcript	c.1151-4G>A	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.1496-4G>A	splice_region_variant, intron_variant		1	NM_005629.4	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000430077.6 linkuse as main transcript	c.1151-4G>A	splice_region_variant, intron_variant		2		ENSP00000403041.2	P48029-4
SLC6A8	ENST00000413787.1 linkuse as main transcript	c.425-4G>A	splice_region_variant, intron_variant		5		ENSP00000400463.1	H7C1I2
SLC6A8	ENST00000485324.1 linkuse as main transcript	n.1799G>A	non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.000108

AC:

AN:

110972

Hom.:

Cov.:

AF XY:

0.0000602

AC XY:

AN XY:

33198

show subpopulations

Gnomad AFR

AF:

0.0000658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.000152

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000984

AC:

AN:

182957

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

67757

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

222

AN:

1094752

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

360490

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.000108

AC:

AN:

111024

Hom.:

Cov.:

AF XY:

0.0000601

AC XY:

AN XY:

33260

show subpopulations

Gnomad4 AFR

AF:

0.0000656

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000718

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 28, 2016

- -

Creatine transporter deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

SLC6A8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2024

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.060

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000075

dbscSNV1_RF

Benign

0.16

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