chrX-153694736-C-T

Variant names:

• chrX-153694736-C-T
• rs369726574
• NM_005629.4:c.1614C>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.1614C>T​(p.Asn538Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000794 in 1,209,721 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 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 0.000018 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000086 (0 hom. 28 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.16
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-153694736-C-T is Benign according to our data. Variant chrX-153694736-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 384044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 28 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.1614C>T	p.Asn538Asn	synonymous	Exon 12 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1584C>T	p.Asn528Asn	synonymous	Exon 12 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1269C>T	p.Asn423Asn	synonymous	Exon 12 of 13	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.1614C>T	p.Asn538Asn	synonymous	Exon 12 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1611C>T	p.Asn537Asn	synonymous	Exon 12 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1605C>T	p.Asn535Asn	synonymous	Exon 12 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112511 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000657 AC: 12 AN: 182585 AF XY: 0.0000887

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000861

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000857 AC: 94 AN: 1097210 Hom.: 0 Cov.: 37 AF XY: 0.0000771 AC XY: 28 AN XY: 362996

African (AFR) AF: 0.00 AC: 0 AN: 26374

American (AMR) AF: 0.0000852 AC: 3 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.000232 AC: 7 AN: 30206

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54109

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3591

European-Non Finnish (NFE) AF: 0.0000962 AC: 81 AN: 841945

Other (OTH) AF: 0.0000435 AC: 2 AN: 46027

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112511 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 34683

African (AFR) AF: 0.00 AC: 0 AN: 30998

American (AMR) AF: 0.00 AC: 0 AN: 10745

Ashkenazi Jewish (ASJ) AF: 0.000377 AC: 1 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.00 AC: 0 AN: 2771

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6193

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53148

Other (OTH) AF: 0.00 AC: 0 AN: 1516

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000491

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Creatine transporter deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.35
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs369726574; hg19: chrX-152960191;