X-153688586-G-T

Variant names:

• chrX-153688586-G-T
• rs1486125548
• NM_005629.4:c.12G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005629.4(SLC6A8):​c.12G>T​(p.Lys4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K4R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000011 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A8 NM_005629.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13751236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.12G>T	p.Lys4Asn	missense_variant	Exon 1 of 13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.12G>T	p.Lys4Asn	missense_variant	Exon 1 of 13		NP_001136277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.12G>T	p.Lys4Asn	missense_variant	Exon 1 of 13	1	NM_005629.4	ENSP00000253122.5
PNCK	ENST00000458354.5	c.-3+229C>A		intron_variant	Intron 1 of 3	3		ENSP00000401542.1
PNCK	ENST00000480693.1	n.64+229C>A		intron_variant	Intron 1 of 3	5
SLC6A8	ENST00000476466.1	n.-137G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000107 AC: 1 AN: 937793 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 296837

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: 0.0000321

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.11
Sift	Benign	0.23	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.22		Loss of ubiquitination at K4 (P = 0.0067);
MVP		0.35
MPC		1.4
ClinPred		0.11	T
GERP RS		2.6
Varity_R		0.18
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs1486125548; hg19: chrX-152954041;