rs151335200

Variant names:

• chrX-153694552-C-G
• rs151335200
• NM_005629.4:c.1515C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-153694552-C-G
• chrX-153694552-C-T
• chrX-153694552-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005629.4(SLC6A8):​c.1515C>G​(p.Asp505Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D505D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SLC6A8 NM_005629.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.75
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32609528).

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.1515C>G	p.Asp505Glu	missense	Exon 11 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1485C>G	p.Asp495Glu	missense	Exon 11 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1170C>G	p.Asp390Glu	missense	Exon 11 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.1515C>G	p.Asp505Glu	missense	Exon 11 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1512C>G	p.Asp504Glu	missense	Exon 11 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1506C>G	p.Asp502Glu	missense	Exon 11 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.075
DANN	Benign	0.97
DEOGEN2	Uncertain	0.42	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.7	L
PhyloP100		-5.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.29
Sift	Benign	0.048	D
Sift4G	Benign	0.10	T
Polyphen		0.81	P
Vest4		0.19
MutPred		0.45		Loss of stability (P = 0.3484)
MVP		0.60
MPC		0.53
ClinPred		0.93	D
GERP RS		-8.1
Varity_R		0.32
gMVP		0.84
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs151335200; hg19: chrX-152960007;