rs201581661
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_005629.4(SLC6A8):c.777+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,197,742 control chromosomes in the GnomAD database, including 1 homozygotes. There are 274 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 0.00057 ( 0 hom., 16 hem., cov: 24)
Exomes 𝑓: 0.00074 ( 1 hom. 258 hem. )
Consequence
SLC6A8
NM_005629.4 splice_donor_region, intron
NM_005629.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.001010
2
Clinical Significance
Conservation
PhyloP100: -0.793
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant X-153692111-C-T is Benign according to our data. Variant chrX-153692111-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 380584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153692111-C-T is described in Lovd as [Benign]. Variant chrX-153692111-C-T is described in Lovd as [Likely_benign].
BS2
?
High Hemizygotes in GnomAd4 at 16 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.777+4C>T | splice_donor_region_variant, intron_variant | ENST00000253122.10 | |||
SLC6A8 | NM_001142805.2 | c.777+4C>T | splice_donor_region_variant, intron_variant | ||||
SLC6A8 | NM_001142806.1 | c.432+4C>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.777+4C>T | splice_donor_region_variant, intron_variant | 1 | NM_005629.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000569 AC: 64AN: 112396Hom.: 0 Cov.: 24 AF XY: 0.000463 AC XY: 16AN XY: 34592
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GnomAD3 exomes AF: 0.000538 AC: 88AN: 163556Hom.: 1 AF XY: 0.000545 AC XY: 28AN XY: 51378
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GnomAD4 exome AF: 0.000742 AC: 805AN: 1085346Hom.: 1 Cov.: 30 AF XY: 0.000732 AC XY: 258AN XY: 352486
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GnomAD4 genome ? AF: 0.000569 AC: 64AN: 112396Hom.: 0 Cov.: 24 AF XY: 0.000463 AC XY: 16AN XY: 34592
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 28, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | SLC6A8: BP4, BS2 - |
Creatine transporter deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
SLC6A8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2016 | 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at