rs384573

Variant names:

• chrX-153688570-A-G
• rs384573
• NM_005629.4:c.-5A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-153688570-A-G
• chrX-153688570-A-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_005629.4(SLC6A8):​c.-5A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene SLC6A8 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 1.0 (37467 hom., 26651 hem., cov: 18)
  • Exomes 𝑓: 1.0 (312231 hom. 283695 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A8 NM_005629.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15 O:1
• Conservation: PhyloP100: 2.25
• Publications: 7 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]

PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

ACMG classification

Specifications for SLC6A8 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-153688570-A-G is Benign according to our data. Variant chrX-153688570-A-G is described in ClinVar as Benign. ClinVar VariationId is 130355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.-5A>G		5_prime_UTR	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.-5A>G		5_prime_UTR	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.-5A>G		5_prime_UTR	Exon 1 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.-5A>G		5_prime_UTR	Exon 1 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.-5A>G		5_prime_UTR	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 101596 AN: 101596 Hom.: 37478 Cov.: 18

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 46799 AN: 46805 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 908179 AN: 908201 Hom.: 312231 Cov.: 17 AF XY: 1.00 AC XY: 283695 AN XY: 283695

African (AFR) AF: 1.00 AC: 18260 AN: 18260

American (AMR) AF: 1.00 AC: 15353 AN: 15357

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 13908 AN: 13908

East Asian (EAS) AF: 1.00 AC: 16577 AN: 16577

South Asian (SAS) AF: 1.00 AC: 38415 AN: 38416

European-Finnish (FIN) AF: 1.00 AC: 28559 AN: 28560

Middle Eastern (MID) AF: 1.00 AC: 2284 AN: 2284

European-Non Finnish (NFE) AF: 1.00 AC: 739086 AN: 739100

Other (OTH) AF: 1.00 AC: 35737 AN: 35739

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 101585 AN: 101585 Hom.: 37467 Cov.: 18 AF XY: 1.00 AC XY: 26651 AN XY: 26651

African (AFR) AF: 1.00 AC: 28352 AN: 28352

American (AMR) AF: 1.00 AC: 9955 AN: 9955

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2509 AN: 2509

East Asian (EAS) AF: 1.00 AC: 3063 AN: 3063

South Asian (SAS) AF: 1.00 AC: 2281 AN: 2281

European-Finnish (FIN) AF: 1.00 AC: 3800 AN: 3800

Middle Eastern (MID) AF: 1.00 AC: 195 AN: 195

European-Non Finnish (NFE) AF: 1.00 AC: 49434 AN: 49434

Other (OTH) AF: 1.00 AC: 1391 AN: 1391

Alfa AF: 1.00 Hom.: 5398

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	not provided (4)
-	-	3	Creatine transporter deficiency (4)
-	-	1	Creatine deficiency syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	SLC6A8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		2.3
PromoterAI		-0.028	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs384573; hg19: chrX-152954025; COSMIC: COSV108056444;