rs144252036
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_005629.4(SLC6A8):c.1020C>T(p.Asp340Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000736 in 1,209,311 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 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 0.00022 ( 0 hom., 4 hem., cov: 24)
Exomes 𝑓: 0.000058 ( 0 hom. 17 hem. )
Consequence
SLC6A8
NM_005629.4 synonymous
NM_005629.4 synonymous
Scores
1
1
8
Clinical Significance
Conservation
PhyloP100: -1.55
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.07809362).
BP6
Variant X-153693465-C-T is Benign according to our data. Variant chrX-153693465-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 379434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.55 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC6A8 | NM_005629.4 | c.1020C>T | p.Asp340Asp | synonymous_variant | 7/13 | ENST00000253122.10 | NP_005620.1 | |
SLC6A8 | NM_001142806.1 | c.675C>T | p.Asp225Asp | synonymous_variant | 7/13 | NP_001136278.1 | ||
SLC6A8 | NM_001142805.2 | c.1017-27C>T | intron_variant | NP_001136277.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC6A8 | ENST00000253122.10 | c.1020C>T | p.Asp340Asp | synonymous_variant | 7/13 | 1 | NM_005629.4 | ENSP00000253122.5 |
Frequencies
GnomAD3 genomes AF: 0.000224 AC: 25AN: 111684Hom.: 0 Cov.: 24 AF XY: 0.000118 AC XY: 4AN XY: 33852
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GnomAD3 exomes AF: 0.000125 AC: 23AN: 183363Hom.: 0 AF XY: 0.0000884 AC XY: 6AN XY: 67881
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GnomAD4 exome AF: 0.0000583 AC: 64AN: 1097577Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 17AN XY: 362975
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GnomAD4 genome AF: 0.000224 AC: 25AN: 111734Hom.: 0 Cov.: 24 AF XY: 0.000118 AC XY: 4AN XY: 33912
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Creatine transporter deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2019 | 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 | May 25, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T
MetaSVM
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift4G
Uncertain
D
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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