X-153694403-C-T

Variant names:

• chrX-153694403-C-T
• rs376421364
• NM_005629.4:c.1452C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_005629.4(SLC6A8):​c.1452C>T​(p.Leu484Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,271 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L484L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.574
• 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-153694403-C-T is Benign according to our data. Variant chrX-153694403-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1583866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.574 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.1452C>T	p.Leu484Leu	synonymous_variant	Exon 10 of 13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.1422C>T	p.Leu474Leu	synonymous_variant	Exon 10 of 13		NP_001136277.1
SLC6A8	NM_001142806.1	c.1107C>T	p.Leu369Leu	synonymous_variant	Exon 10 of 13		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1452C>T	p.Leu484Leu	synonymous_variant	Exon 10 of 13	1	NM_005629.4	ENSP00000253122.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097271 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 362753

African (AFR) AF: 0.00 AC: 0 AN: 26386

American (AMR) AF: 0.0000284 AC: 1 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40495

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841297

Other (OTH) AF: 0.00 AC: 0 AN: 46062

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Creatine transporter deficiency Benign:1

Aug 15, 2022

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	-0.51
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		-0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs376421364; hg19: chrX-152959858;