rs782682148

chrX-153695062-CCT-CchrX-153695062-CCT-CCTCT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_005629.4(SLC6A8):c.1768-8_1768-7del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,196,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: SLC6A8 NM_005629.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.198

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-153695062-CCT-C is Benign according to our data. Variant chrX-153695062-CCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 533701.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.1768-8_1768-7del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000253122.10
SLC6A8	NM_001142805.2	c.1738-8_1738-7del		splice_polypyrimidine_tract_variant, intron_variant
SLC6A8	NM_001142806.1	c.1423-8_1423-7del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1768-8_1768-7del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005629.4	P1
SLC6A8	ENST00000430077.6	c.1423-8_1423-7del		splice_polypyrimidine_tract_variant, intron_variant		2
SLC6A8	ENST00000485324.1	n.2075-8_2075-7del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000887 AC: 1 AN: 112688 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34846

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000929

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: 0.00

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083975 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 353255

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000294

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 AF: 0.00000887 AC: 1 AN: 112688 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34846

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000929

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: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Creatine transporter deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs782682148; hg19: chrX-152960517;