X-153694165-C-T

Variant names:

• chrX-153694165-C-T
• rs782667574
• NM_005629.4:c.1290C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4 BP6_Very_Strong BP7 BS2

The NM_005629.4(SLC6A8):​c.1290C>T​(p.Leu430Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,208,539 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000028 (0 hom. 8 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.234
• 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, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.282).
• BP6: Variant X-153694165-C-T is Benign according to our data. Variant chrX-153694165-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 515345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 8 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.1290C>T	p.Leu430Leu	synonymous	Exon 9 of 13	NP_005620.1
	SLC6A8	NM_001142805.2		c.1260C>T	p.Leu420Leu	synonymous	Exon 9 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.945C>T	p.Leu315Leu	synonymous	Exon 9 of 13	NP_001136278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.1290C>T	p.Leu430Leu	synonymous	Exon 9 of 13	ENSP00000253122.5
	SLC6A8	ENST00000955775.1		c.1290C>T	p.Leu430Leu	synonymous	Exon 9 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1290C>T	p.Leu430Leu	synonymous	Exon 9 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111580 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000273 AC: 5 AN: 183013 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000283 AC: 31 AN: 1096959 Hom.: 0 Cov.: 34 AF XY: 0.0000221 AC XY: 8 AN XY: 362485

African (AFR) AF: 0.0000379 AC: 1 AN: 26383

American (AMR) AF: 0.000114 AC: 4 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54117

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40469

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4115

European-Non Finnish (NFE) AF: 0.0000273 AC: 23 AN: 841047

Other (OTH) AF: 0.0000434 AC: 2 AN: 46052

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111580 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33776

African (AFR) AF: 0.00 AC: 0 AN: 30655

American (AMR) AF: 0.00 AC: 0 AN: 10595

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6065

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53011

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: 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 specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.5
DANN	Benign	0.68
PhyloP100		-0.23
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)		0.080		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: rs782667574; hg19: chrX-152959620;