rs782114947
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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.1533C>T(p.Ile511Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,129,538 control chromosomes in the GnomAD database, including 1 homozygotes. There are 37 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 0.00011 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.00011 ( 1 hom. 35 hem. )
Consequence
SLC6A8
NM_005629.4 synonymous
NM_005629.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.33
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=-0.63).
BP6
Variant X-153694570-C-T is Benign according to our data. Variant chrX-153694570-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 385282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.33 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.1533C>T | p.Ile511Ile | synonymous_variant | 11/13 | ENST00000253122.10 | NP_005620.1 | |
SLC6A8 | NM_001142805.2 | c.1503C>T | p.Ile501Ile | synonymous_variant | 11/13 | NP_001136277.1 | ||
SLC6A8 | NM_001142806.1 | c.1188C>T | p.Ile396Ile | synonymous_variant | 11/13 | NP_001136278.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.1533C>T | p.Ile511Ile | synonymous_variant | 11/13 | 1 | NM_005629.4 | ENSP00000253122.5 | ||
SLC6A8 | ENST00000430077.6 | c.1188C>T | p.Ile396Ile | synonymous_variant | 11/13 | 2 | ENSP00000403041.2 | |||
SLC6A8 | ENST00000413787.1 | c.462C>T | p.Ile154Ile | synonymous_variant | 6/6 | 5 | ENSP00000400463.1 | |||
SLC6A8 | ENST00000485324.1 | n.1840C>T | non_coding_transcript_exon_variant | 4/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 11AN: 104734Hom.: 0 Cov.: 22 AF XY: 0.0000665 AC XY: 2AN XY: 30072
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GnomAD3 exomes AF: 0.000104 AC: 19AN: 183059Hom.: 0 AF XY: 0.0000737 AC XY: 5AN XY: 67803
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GnomAD4 exome AF: 0.000109 AC: 112AN: 1024804Hom.: 1 Cov.: 34 AF XY: 0.000105 AC XY: 35AN XY: 334710
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GnomAD4 genome AF: 0.000105 AC: 11AN: 104734Hom.: 0 Cov.: 22 AF XY: 0.0000665 AC XY: 2AN XY: 30072
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
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 | May 05, 2016 | - - |
Creatine transporter deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Creatine deficiency syndrome 1 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 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 | Mar 08, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at