rs782114947

chrX-153694570-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005629.4(SLC6A8):c.1533C>T(p.Ile511=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,129,538 control chromosomes in the GnomAD database, including 1 homozygotes. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.00011 (1 hom. 35 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.33

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant X-153694570-C-T is Benign according to our data. Variant chrX-153694570-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 385282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.33 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.1533C>T	p.Ile511=	synonymous_variant	11/13	ENST00000253122.10
SLC6A8	NM_001142805.2	c.1503C>T	p.Ile501=	synonymous_variant	11/13
SLC6A8	NM_001142806.1	c.1188C>T	p.Ile396=	synonymous_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1533C>T	p.Ile511=	synonymous_variant	11/13	1	NM_005629.4	P1
SLC6A8	ENST00000430077.6	c.1188C>T	p.Ile396=	synonymous_variant	11/13	2
SLC6A8	ENST00000413787.1	c.462C>T	p.Ile154=	synonymous_variant	6/6	5
SLC6A8	ENST00000485324.1	n.1840C>T		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 11 AN: 104734 Hom.: 0 Cov.: 22 AF XY: 0.0000665 AC XY: 2 AN XY: 30072

Gnomad AFR AF: 0.000172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000202

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000344

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000104 AC: 19 AN: 183059 Hom.: 0 AF XY: 0.0000737 AC XY: 5 AN XY: 67803

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.0000730

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000289

Gnomad SAS exome AF: 0.000157

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000858

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.000109 AC: 112 AN: 1024804 Hom.: 1 Cov.: 34 AF XY: 0.000105 AC XY: 35 AN XY: 334710

Gnomad4 AFR exome AF: 0.000124

Gnomad4 AMR exome AF: 0.0000609

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000212

Gnomad4 SAS exome AF: 0.0000936

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000956

Gnomad4 OTH exome AF: 0.000510

GnomAD4 genome AF: 0.000105 AC: 11 AN: 104734 Hom.: 0 Cov.: 22 AF XY: 0.0000665 AC XY: 2 AN XY: 30072

Gnomad4 AFR AF: 0.000172

Gnomad4 AMR AF: 0.000202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000344

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000178

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 05, 2016

- -

Creatine transporter deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Creatine deficiency syndrome 1 Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2017

This alteration is classified as likely 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. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	1.7
Dann	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs782114947; hg19: chrX-152960025; COSMIC: COSV99466008; COSMIC: COSV99466008;