rs1557045581

Positions:

• chrX-153694616-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_005629.4(SLC6A8):​c.1583delC​(p.Pro528fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A8 NM_005629.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.92

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-153694616-AC-A is Pathogenic according to our data. Variant chrX-153694616-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 436772.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.1583delC	p.Pro528fs	frameshift_variant	11/13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.1553delC	p.Pro518fs	frameshift_variant	11/13		NP_001136277.1
SLC6A8	NM_001142806.1	c.1238delC	p.Pro413fs	frameshift_variant	11/13		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1583delC	p.Pro528fs	frameshift_variant	11/13	1	NM_005629.4	ENSP00000253122.5
SLC6A8	ENST00000430077.6	c.1238delC	p.Pro413fs	frameshift_variant	11/13	2		ENSP00000403041.2
SLC6A8	ENST00000485324.1	n.1890delC		non_coding_transcript_exon_variant	4/6	2
SLC6A8	ENST00000413787.1	c.*41delC		downstream_gene_variant		5		ENSP00000400463.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 874531 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 274977

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Creatine transporter deficiency Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 30, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1557045581; hg19: chrX-152960071;