chrX-153688580-G-A

Variant names:

• chrX-153688580-G-A
• rs1557043713
• NM_005629.4:c.6G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005629.4(SLC6A8):​c.6G>A​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,032,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000096 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.0000043 (0 hom. 3 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-153688580-G-A is Benign according to our data. Variant chrX-153688580-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2064955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.27 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.6G>A	p.Ala2Ala	synonymous	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.6G>A	p.Ala2Ala	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.6G>A	p.Ala2Ala	synonymous	Exon 1 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.00000957 AC: 1 AN: 104474 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

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: 0.0000199

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 51827 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000431 AC: 4 AN: 927550 Hom.: 0 Cov.: 22 AF XY: 0.0000103 AC XY: 3 AN XY: 291750

African (AFR) AF: 0.00 AC: 0 AN: 18911

American (AMR) AF: 0.00 AC: 0 AN: 16893

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14594

East Asian (EAS) AF: 0.00 AC: 0 AN: 17470

South Asian (SAS) AF: 0.00 AC: 0 AN: 39899

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30301

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2388

European-Non Finnish (NFE) AF: 0.00000400 AC: 3 AN: 750188

Other (OTH) AF: 0.0000271 AC: 1 AN: 36906

GnomAD4 genome AF: 0.00000957 AC: 1 AN: 104474 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 28856

⚠️ 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: 29106

American (AMR) AF: 0.00 AC: 0 AN: 10176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2549

East Asian (EAS) AF: 0.00 AC: 0 AN: 3167

South Asian (SAS) AF: 0.00 AC: 0 AN: 2436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.0000199 AC: 1 AN: 50310

Other (OTH) AF: 0.00 AC: 0 AN: 1417

⚠️ 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

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		1.3
PromoterAI		-0.075	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: rs1557043713; hg19: chrX-152954035;