rs782517934

chrX-153693325-A-C

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.975A>C(p.Thr325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000612 in 1,209,647 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 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 0.000036 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000064 (0 hom. 23 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.49

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_addAF=-0.656634).
• BP6: Variant X-153693325-A-C is Benign according to our data. Variant chrX-153693325-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 416006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAdExome at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.975A>C	p.Thr325=	synonymous_variant	6/13	ENST00000253122.10
SLC6A8	NM_001142805.2	c.975A>C	p.Thr325=	synonymous_variant	6/13
SLC6A8	NM_001142806.1	c.630A>C	p.Thr210=	synonymous_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.975A>C	p.Thr325=	synonymous_variant	6/13	1	NM_005629.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000357 AC: 4 AN: 112161 Hom.: 0 Cov.: 24 AF XY: 0.0000291 AC XY: 1 AN XY: 34359

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000936

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: 0.0000565

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000131 AC: 24 AN: 182997 Hom.: 0 AF XY: 0.000118 AC XY: 8 AN XY: 67789

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000219

Gnomad ASJ exome AF: 0.000669

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.0000638 AC: 70 AN: 1097433 Hom.: 0 Cov.: 32 AF XY: 0.0000634 AC XY: 23 AN XY: 362831

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.000170

Gnomad4 ASJ exome AF: 0.000671

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000428

Gnomad4 OTH exome AF: 0.000130

GnomAD4 genome AF: 0.0000356 AC: 4 AN: 112214 Hom.: 0 Cov.: 24 AF XY: 0.0000291 AC XY: 1 AN XY: 34422

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000935

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000565

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000718

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	SLC6A8: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 14, 2018	- -

Creatine transporter deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.1
Dann	Benign	0.67
FATHMM_MKL	Benign	0.22	N
MutationTaster	Benign	1.0	D;D
ClinPred		0.24	T
GERP RS		-10
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782517934; hg19: chrX-152958780;