rs782589547

chrX-153694529-G-AchrX-153694529-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005629.4(SLC6A8):c.1496-4G>A variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00007542
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.71

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 -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 GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.1496-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000253122.10
SLC6A8	NM_001142805.2	c.1466-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SLC6A8	NM_001142806.1	c.1151-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1496-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005629.4	P1
SLC6A8	ENST00000413787.1	c.425-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
SLC6A8	ENST00000430077.6	c.1151-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
SLC6A8	ENST00000485324.1	n.1799G>A		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 12 AN: 110972 Hom.: 0 Cov.: 23 AF XY: 0.0000602 AC XY: 2 AN XY: 33198

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: 18 AN: 182957 Hom.: 0 AF XY: 0.000177 AC XY: 12 AN XY: 67757

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.: 0 Cov.: 34 AF XY: 0.000205 AC XY: 74 AN XY: 360490

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: 12 AN: 111024 Hom.: 0 Cov.: 23 AF XY: 0.0000601 AC XY: 2 AN XY: 33260

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.: 0

Bravo AF: 0.0000718

EpiCase AF: 0.000491

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

Jun 28, 2016

- -

Creatine transporter deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

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

Other links and lift over

dbSNP: rs782589547; hg19: chrX-152959984;