rs782682148

Variant names:

• chrX-153695062-CCT-C
• rs782682148
• NM_005629.4:c.1768-8_1768-7delTC

Your query was ambiguous. Multiple possible variants found:

• chrX-153695062-CCT-C
• chrX-153695062-CCT-CCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_005629.4(SLC6A8):​c.1768-8_1768-7delTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,196,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: SLC6A8 NM_005629.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.198
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-153695062-CCT-C is Benign according to our data. Variant chrX-153695062-CCT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 533701.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1768-8_1768-7delTC		splice_region intron	N/A	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1738-8_1738-7delTC		splice_region intron	N/A	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1423-8_1423-7delTC		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.1768-11_1768-10delCT		intron	N/A	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1765-11_1765-10delCT		intron	N/A	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1759-11_1759-10delCT		intron	N/A	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.00000887 AC: 1 AN: 112688 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000929

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

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083975 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 353255

African (AFR) AF: 0.00 AC: 0 AN: 26147

American (AMR) AF: 0.0000294 AC: 1 AN: 34010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19027

East Asian (EAS) AF: 0.00 AC: 0 AN: 29642

South Asian (SAS) AF: 0.00 AC: 0 AN: 52082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39269

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834594

Other (OTH) AF: 0.00 AC: 0 AN: 45462

GnomAD4 genome AF: 0.00000887 AC: 1 AN: 112688 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34846

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30977

American (AMR) AF: 0.0000929 AC: 1 AN: 10765

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3581

South Asian (SAS) AF: 0.00 AC: 0 AN: 2749

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6285

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53242

Other (OTH) AF: 0.00 AC: 0 AN: 1512

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs782682148; hg19: chrX-152960517;