X-153693076-C-G

Variant names:

• chrX-153693076-C-G
• NM_005629.4:c.813C>G
• SLC6A8 p.Val271Val

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005629.4(SLC6A8):​c.813C>G​(p.Val271Val) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. V271V) has been classified as Likely benign. The gene SLC6A8 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 24)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, G2P, Orphanet

ACMG classification

Specifications for SLC6A8 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1754503).
• BP7: Synonymous conserved (PhyloP=0.488 with no splicing effect.

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.813C>G	p.Val271Val	synonymous	Exon 5 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.813C>G	p.Val271Val	synonymous	Exon 5 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.468C>G	p.Val156Val	synonymous	Exon 5 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.813C>G	p.Val271Val	synonymous	Exon 5 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000413787.1	TSL:5	c.23C>G	p.Ser8Cys	missense	Exon 1 of 6	ENSP00000400463.1	H7C1I2
	SLC6A8	ENST00000955775.1		c.813C>G	p.Val271Val	synonymous	Exon 5 of 13	ENSP00000625834.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	11
DANN	Benign	0.86
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.21	T
PhyloP100		0.49
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.9
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-152958531;