X-153695194-G-C

Variant names:

• chrX-153695194-G-C
• NM_005629.4:c.1888G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005629.4(SLC6A8):​c.1888G>C​(p.Val630Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000932 in 1,072,403 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. 12/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V630M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: SLC6A8 NM_005629.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047998518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.1888G>C	p.Val630Leu	missense_variant	Exon 13 of 13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.1858G>C	p.Val620Leu	missense_variant	Exon 13 of 13		NP_001136277.1
SLC6A8	NM_001142806.1	c.1543G>C	p.Val515Leu	missense_variant	Exon 13 of 13		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1888G>C	p.Val630Leu	missense_variant	Exon 13 of 13	1	NM_005629.4	ENSP00000253122.5
SLC6A8	ENST00000430077.6	c.1543G>C	p.Val515Leu	missense_variant	Exon 13 of 13	2		ENSP00000403041.2
SLC6A8	ENST00000485324.1	n.2195G>C		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.32e-7 AC: 1 AN: 1072403 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 348481

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.45
DEOGEN2	Benign	0.096	T;.
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.20	N;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.094
Sift	Benign	0.77	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0020	B;.
Vest4		0.025
MutPred		0.21		Loss of catalytic residue at V630 (P = 0.0071);.;
MVP		0.068
MPC		0.15
ClinPred		0.39	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.092
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152960649;