chrX-153691562-G-C

Variant names:

• chrX-153691562-G-C
• rs200353790
• NM_005629.4:c.644+9G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005629.4(SLC6A8):​c.644+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,209,866 control chromosomes in the GnomAD database, including 1 homozygotes. There are 3 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 0.000071 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000010 (1 hom. 2 hem.)
• Consequence: SLC6A8 NM_005629.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0680
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant X-153691562-G-C is Benign according to our data. Variant chrX-153691562-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 702153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.644+9G>C		intron	N/A	NP_005620.1
	SLC6A8	NM_001142805.2		c.644+9G>C		intron	N/A	NP_001136277.1
	SLC6A8	NM_001142806.1		c.299+9G>C		intron	N/A	NP_001136278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.644+9G>C		intron	N/A	ENSP00000253122.5
	SLC6A8	ENST00000430077.6	TSL:2	c.299+9G>C		intron	N/A	ENSP00000403041.2
	SLC6A8	ENST00000429147.1	TSL:2	c.92+9G>C		intron	N/A	ENSP00000404046.1

Frequencies

GnomAD3 genomes AF: 0.0000706 AC: 8 AN: 113309 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000256

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000222 AC: 4 AN: 180354 AF XY: 0.00

Gnomad AFR exome AF: 0.000309

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: 0.0000100 AC: 11 AN: 1096557 Hom.: 1 Cov.: 31 AF XY: 0.00000552 AC XY: 2 AN XY: 362545

African (AFR) AF: 0.000417 AC: 11 AN: 26377

American (AMR) AF: 0.00 AC: 0 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.00 AC: 0 AN: 54103

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39937

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3916

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841439

Other (OTH) AF: 0.00 AC: 0 AN: 46033

GnomAD4 genome AF: 0.0000706 AC: 8 AN: 113309 Hom.: 0 Cov.: 24 AF XY: 0.0000282 AC XY: 1 AN XY: 35461

African (AFR) AF: 0.000256 AC: 8 AN: 31232

American (AMR) AF: 0.00 AC: 0 AN: 10856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3600

South Asian (SAS) AF: 0.00 AC: 0 AN: 2829

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6358

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53321

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Creatine transporter deficiency Benign:1

Jun 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.2
DANN	Benign	0.73
PhyloP100		-0.068
PromoterAI		0.0080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs200353790; hg19: chrX-152957017;