rs151335200

chrX-153694552-C-AchrX-153694552-C-GchrX-153694552-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005629.4(SLC6A8):c.1515C>A(p.Asp505Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 110,276 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. D505D) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 22)
• Consequence: SLC6A8 NM_005629.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23056585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.1515C>A	p.Asp505Glu	missense_variant	11/13	ENST00000253122.10
SLC6A8	NM_001142805.2	c.1485C>A	p.Asp495Glu	missense_variant	11/13
SLC6A8	NM_001142806.1	c.1170C>A	p.Asp390Glu	missense_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1515C>A	p.Asp505Glu	missense_variant	11/13	1	NM_005629.4	P1
SLC6A8	ENST00000430077.6	c.1170C>A	p.Asp390Glu	missense_variant	11/13	2
SLC6A8	ENST00000413787.1	c.444C>A	p.Asp148Glu	missense_variant	6/6	5
SLC6A8	ENST00000485324.1	n.1822C>A		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.00000907 AC: 1 AN: 110276 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32530

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: 0.0000190

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000907 AC: 1 AN: 110276 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32530

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000190

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	0.070
Dann	Benign	0.97
DEOGEN2	Uncertain	0.42	T;.;.
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	0.86	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.048	D;T;T
Sift4G	Benign	0.10	T;T;D
Polyphen		0.81	P;.;.
Vest4		0.19
MutPred		0.45		Loss of stability (P = 0.3484);.;.;
MVP		0.60
MPC		0.53
ClinPred		0.49	T
GERP RS		-8.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs151335200; hg19: chrX-152960007;