X-153694835-C-T

Variant names:

• chrX-153694835-C-T
• rs782244505
• NM_005629.4:c.1713C>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.1713C>T​(p.Cys571Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,207,372 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 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 0.000062 (0 hom., 2 hem., cov: 25)
  • Exomes 𝑓: 0.00012 (0 hom. 45 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.148
• 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 (BayesDel_noAF=-0.46).
• BP6: Variant X-153694835-C-T is Benign according to our data. Variant chrX-153694835-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.148 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 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.1713C>T	p.Cys571Cys	synonymous	Exon 12 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1683C>T	p.Cys561Cys	synonymous	Exon 12 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1368C>T	p.Cys456Cys	synonymous	Exon 12 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.1713C>T	p.Cys571Cys	synonymous	Exon 12 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1710C>T	p.Cys570Cys	synonymous	Exon 12 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1704C>T	p.Cys568Cys	synonymous	Exon 12 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.0000619 AC: 7 AN: 113004 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000926

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000558

Gnomad SAS AF: 0.000710

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000210 AC: 37 AN: 176273 AF XY: 0.000225

Gnomad AFR exome AF: 0.0000797

Gnomad AMR exome AF: 0.000259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000643

Gnomad OTH exome AF: 0.000683

GnomAD4 exome AF: 0.000118 AC: 129 AN: 1094368 Hom.: 0 Cov.: 37 AF XY: 0.000125 AC XY: 45 AN XY: 360656

African (AFR) AF: 0.000114 AC: 3 AN: 26339

American (AMR) AF: 0.000114 AC: 4 AN: 35020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.000365 AC: 11 AN: 30168

South Asian (SAS) AF: 0.000913 AC: 49 AN: 53696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3373

European-Non Finnish (NFE) AF: 0.0000547 AC: 46 AN: 840545

Other (OTH) AF: 0.000349 AC: 16 AN: 45908

GnomAD4 genome AF: 0.0000619 AC: 7 AN: 113004 Hom.: 0 Cov.: 25 AF XY: 0.0000569 AC XY: 2 AN XY: 35158

African (AFR) AF: 0.0000321 AC: 1 AN: 31152

American (AMR) AF: 0.0000926 AC: 1 AN: 10795

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.000558 AC: 2 AN: 3585

South Asian (SAS) AF: 0.000710 AC: 2 AN: 2816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6273

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53277

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.000151

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.66
DANN	Benign	0.64
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs782244505; hg19: chrX-152960290;