X-153694715-G-C

Variant names:

• chrX-153694715-G-C
• rs1312663828
• NM_005629.4:c.1597-4G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005629.4(SLC6A8):​c.1597-4G>C variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: SLC6A8 NM_005629.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001591
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.97

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-153694715-G-C is Benign according to our data. Variant chrX-153694715-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2753742.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.1597-4G>C		splice_region_variant, intron_variant	Intron 11 of 12	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.1567-4G>C		splice_region_variant, intron_variant	Intron 11 of 12		NP_001136277.1
SLC6A8	NM_001142806.1	c.1252-4G>C		splice_region_variant, intron_variant	Intron 11 of 12		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1597-4G>C		splice_region_variant, intron_variant	Intron 11 of 12	1	NM_005629.4	ENSP00000253122.5
SLC6A8	ENST00000430077.6	c.1252-4G>C		splice_region_variant, intron_variant	Intron 11 of 12	2		ENSP00000403041.2
SLC6A8	ENST00000485324.1	n.1904-4G>C		splice_region_variant, intron_variant	Intron 4 of 5	2
SLC6A8	ENST00000413787.1	c.*139G>C		downstream_gene_variant		5		ENSP00000400463.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Creatine transporter deficiency Benign:1

Aug 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0040
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.056
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: rs1312663828; hg19: chrX-152960170;