rs200695210

Variant names:

• chrX-153694528-C-T
• rs200695210
• NM_005629.4:c.1496-5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005629.4(SLC6A8):​c.1496-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,205,694 control chromosomes in the GnomAD database, including 4 homozygotes. There are 332 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., 134 hem., cov: 23)
  • Exomes 𝑓: 0.00064 (0 hom. 198 hem.)
• Consequence: SLC6A8 NM_005629.4 splice_region, intron
• Scores: Splicing: ADA: 0.00004396
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.414
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-153694528-C-T is Benign according to our data. Variant chrX-153694528-C-T is described in ClinVar as Benign. ClinVar VariationId is 383235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00449 (499/111068) while in subpopulation AFR AF = 0.0155 (473/30490). AF 95% confidence interval is 0.0144. There are 4 homozygotes in GnomAd4. There are 134 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.1496-5C>T		splice_region intron	N/A	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1466-5C>T		splice_region intron	N/A	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1151-5C>T		splice_region intron	N/A	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.1496-5C>T		splice_region intron	N/A	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1496-8C>T		splice_region intron	N/A	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1487-5C>T		splice_region intron	N/A	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 499 AN: 111016 Hom.: 4 Cov.: 23

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000758

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: 0.000246

Gnomad OTH AF: 0.00333

GnomAD2 exomes AF: 0.00145 AC: 265 AN: 182957 AF XY: 0.000915

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000723

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000184

Gnomad OTH exome AF: 0.000884

GnomAD4 exome AF: 0.000642 AC: 703 AN: 1094626 Hom.: 0 Cov.: 33 AF XY: 0.000549 AC XY: 198 AN XY: 360344

African (AFR) AF: 0.0154 AC: 406 AN: 26314

American (AMR) AF: 0.000909 AC: 32 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19370

East Asian (EAS) AF: 0.000166 AC: 5 AN: 30192

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54062

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40454

Middle Eastern (MID) AF: 0.000488 AC: 2 AN: 4102

European-Non Finnish (NFE) AF: 0.000261 AC: 219 AN: 838976

Other (OTH) AF: 0.000783 AC: 36 AN: 45958

GnomAD4 genome AF: 0.00449 AC: 499 AN: 111068 Hom.: 4 Cov.: 23 AF XY: 0.00403 AC XY: 134 AN XY: 33282

African (AFR) AF: 0.0155 AC: 473 AN: 30490

American (AMR) AF: 0.000757 AC: 8 AN: 10571

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3514

South Asian (SAS) AF: 0.00 AC: 0 AN: 2618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6023

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000246 AC: 13 AN: 52797

Other (OTH) AF: 0.00329 AC: 5 AN: 1522

Alfa AF: 0.00234 Hom.: 9

Bravo AF: 0.00499

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Creatine transporter deficiency (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000044
dbscSNV1_RF	Benign	0.046
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

Other links and lift over

dbSNP: rs200695210; hg19: chrX-152959983;