X-153688604-C-T

Variant names:

• chrX-153688604-C-T
• rs1057522627
• NM_005629.4:c.30C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005629.4(SLC6A8):​c.30C>T​(p.Ile10Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 963,801 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000042 (0 hom. 2 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.733
• 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]

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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-153688604-C-T is Benign according to our data. Variant chrX-153688604-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 386861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.733 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.30C>T	p.Ile10Ile	synonymous	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.30C>T	p.Ile10Ile	synonymous	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.30C>T	p.Ile10Ile	synonymous	Exon 1 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.30C>T	p.Ile10Ile	synonymous	Exon 1 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.30C>T	p.Ile10Ile	synonymous	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000415 AC: 4 AN: 963801 Hom.: 0 Cov.: 25 AF XY: 0.00000648 AC XY: 2 AN XY: 308605

African (AFR) AF: 0.00 AC: 0 AN: 19758

American (AMR) AF: 0.00 AC: 0 AN: 19289

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15576

East Asian (EAS) AF: 0.00 AC: 0 AN: 18982

South Asian (SAS) AF: 0.00 AC: 0 AN: 43432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33123

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2554

European-Non Finnish (NFE) AF: 0.00000389 AC: 3 AN: 772112

Other (OTH) AF: 0.0000257 AC: 1 AN: 38975

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		0.73
PromoterAI		0.015	Neutral

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: rs1057522627; hg19: chrX-152954059;