rs782560726

Variant names:

• chrX-153695084-A-C
• rs782560726
• NM_005629.4:c.1778A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-153695084-A-C
• chrX-153695084-A-G

Variant summary

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

The NM_005629.4(SLC6A8):​c.1778A>C​(p.His593Pro) 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. 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. H593R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SLC6A8 NM_005629.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 1 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, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

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=0.30352658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.1778A>C	p.His593Pro	missense_variant	Exon 13 of 13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.1748A>C	p.His583Pro	missense_variant	Exon 13 of 13		NP_001136277.1
SLC6A8	NM_001142806.1	c.1433A>C	p.His478Pro	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.1778A>C	p.His593Pro	missense_variant	Exon 13 of 13	1	NM_005629.4	ENSP00000253122.5
SLC6A8	ENST00000430077.6	c.1433A>C	p.His478Pro	missense_variant	Exon 13 of 13	2		ENSP00000403041.2
SLC6A8	ENST00000485324.1	n.2085A>C		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.55	N;.
PhyloP100		2.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.21	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.18	B;.
Vest4		0.40
MutPred		0.53		Loss of MoRF binding (P = 0.0716);.;
MVP		0.92
MPC		0.34
ClinPred		0.21	T
GERP RS		5.2
Varity_R		0.58
gMVP		0.95
Mutation Taster		=44/56	disease causing

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

Other links and lift over

dbSNP: rs782560726; hg19: chrX-152960539;