rs781788160

Variant names:

• chrX-153694159-C-T
• rs781788160
• NM_005629.4:c.1284C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005629.4(SLC6A8):​c.1284C>T​(p.Gly428Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,096,757 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 5 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.608
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• creatine transporter deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.048).
• BP6: Variant X-153694159-C-T is Benign according to our data. Variant chrX-153694159-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 533703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.608 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.1284C>T	p.Gly428Gly	synonymous	Exon 9 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1254C>T	p.Gly418Gly	synonymous	Exon 9 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.939C>T	p.Gly313Gly	synonymous	Exon 9 of 13	NP_001136278.1	P48029-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.1284C>T	p.Gly428Gly	synonymous	Exon 9 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1284C>T	p.Gly428Gly	synonymous	Exon 9 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1284C>T	p.Gly428Gly	synonymous	Exon 9 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000219 AC: 4 AN: 182954 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1096757 Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 5 AN XY: 362285

African (AFR) AF: 0.00 AC: 0 AN: 26382

American (AMR) AF: 0.00 AC: 0 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19370

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.000166 AC: 9 AN: 54116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40458

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4107

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840887

Other (OTH) AF: 0.0000434 AC: 2 AN: 46043

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781788160; hg19: chrX-152959614;