rs187400676

chrX-153693604-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005629.4(SLC6A8):c.1141+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,205,279 control chromosomes in the GnomAD database, including 17 homozygotes. There are 758 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 0.0037 (3 hom., 164 hem., cov: 24)
  • Exomes 𝑓: 0.0018 (14 hom. 594 hem.)
• Consequence: SLC6A8 NM_005629.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.95

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-153693604-G-A is Benign according to our data. Variant chrX-153693604-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 381457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153693604-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00374 (422/112828) while in subpopulation AMR AF= 0.031 (333/10738). AF 95% confidence interval is 0.0283. There are 3 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.1141+18G>A		intron_variant		ENST00000253122.10
SLC6A8	NM_001142805.2	c.1111+18G>A		intron_variant
SLC6A8	NM_001142806.1	c.796+18G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1141+18G>A		intron_variant		1	NM_005629.4	P1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 426 AN: 112775 Hom.: 3 Cov.: 24 AF XY: 0.00470 AC XY: 164 AN XY: 34911

Gnomad AFR AF: 0.000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00644

Gnomad SAS AF: 0.000362

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000300

Gnomad OTH AF: 0.00461

GnomAD3 exomes AF: 0.00596 AC: 1088 AN: 182547 Hom.: 9 AF XY: 0.00476 AC XY: 321 AN XY: 67487

Gnomad AFR exome AF: 0.000230

Gnomad AMR exome AF: 0.0310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00484

Gnomad SAS exome AF: 0.000524

Gnomad FIN exome AF: 0.00675

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00184 AC: 2012 AN: 1092451 Hom.: 14 Cov.: 31 AF XY: 0.00166 AC XY: 594 AN XY: 358591

Gnomad4 AFR exome AF: 0.000228

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.000574

Gnomad4 FIN exome AF: 0.00633

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00198

GnomAD4 genome AF: 0.00374 AC: 422 AN: 112828 Hom.: 3 Cov.: 24 AF XY: 0.00469 AC XY: 164 AN XY: 34974

Gnomad4 AFR AF: 0.000321

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.000364

Gnomad4 FIN AF: 0.00529

Gnomad4 NFE AF: 0.000300

Gnomad4 OTH AF: 0.00455

Alfa AF: 0.00182 Hom.: 15

Bravo AF: 0.00578

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Creatine transporter deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.15
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs187400676; hg19: chrX-152959059;