rs201260657
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005629.4(SLC6A8):c.498G>A(p.Thr166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,209,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., 2 hem., cov: 25)
Exomes 𝑓: 0.000056 ( 0 hom. 17 hem. )
Consequence
SLC6A8
NM_005629.4 synonymous
NM_005629.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.891
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant X-153691407-G-A is Benign according to our data. Variant chrX-153691407-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.891 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.498G>A | p.Thr166= | synonymous_variant | 3/13 | ENST00000253122.10 | |
SLC6A8 | NM_001142805.2 | c.498G>A | p.Thr166= | synonymous_variant | 3/13 | ||
SLC6A8 | NM_001142806.1 | c.153G>A | p.Thr51= | synonymous_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.498G>A | p.Thr166= | synonymous_variant | 3/13 | 1 | NM_005629.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000531 AC: 6AN: 112909Hom.: 0 Cov.: 25 AF XY: 0.0000570 AC XY: 2AN XY: 35093
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GnomAD3 exomes AF: 0.0000930 AC: 17AN: 182870Hom.: 0 AF XY: 0.0000739 AC XY: 5AN XY: 67618
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GnomAD4 exome AF: 0.0000556 AC: 61AN: 1096991Hom.: 0 Cov.: 30 AF XY: 0.0000469 AC XY: 17AN XY: 362571
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GnomAD4 genome ? AF: 0.0000531 AC: 6AN: 112959Hom.: 0 Cov.: 25 AF XY: 0.0000569 AC XY: 2AN XY: 35153
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 18, 2019 | - - |
Creatine transporter deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at