rs80338740
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PM1PM2PM4_SupportingPP5_Very_Strong
The NM_005629.4(SLC6A8):c.1222_1224delTTC(p.Phe408del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 112,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Pathogenic (★★★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
SLC6A8
NM_005629.4 conservative_inframe_deletion
NM_005629.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.91
Publications
12 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 deficiencyInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 13 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 9 uncertain in NM_005629.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_005629.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant X-153693978-GTTC-G is Pathogenic according to our data. Variant chrX-153693978-GTTC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 11698.Status of the report is reviewed_by_expert_panel, 3 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005629.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC6A8 | NM_005629.4 | MANE Select | c.1222_1224delTTC | p.Phe408del | conservative_inframe_deletion | Exon 8 of 13 | NP_005620.1 | ||
| SLC6A8 | NM_001142805.2 | c.1192_1194delTTC | p.Phe398del | conservative_inframe_deletion | Exon 8 of 13 | NP_001136277.1 | |||
| SLC6A8 | NM_001142806.1 | c.877_879delTTC | p.Phe293del | conservative_inframe_deletion | Exon 8 of 13 | NP_001136278.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC6A8 | ENST00000253122.10 | TSL:1 MANE Select | c.1222_1224delTTC | p.Phe408del | conservative_inframe_deletion | Exon 8 of 13 | ENSP00000253122.5 | ||
| SLC6A8 | ENST00000430077.6 | TSL:2 | c.877_879delTTC | p.Phe293del | conservative_inframe_deletion | Exon 8 of 13 | ENSP00000403041.2 | ||
| SLC6A8 | ENST00000442457.1 | TSL:3 | c.274_276delTTC | p.Phe92del | conservative_inframe_deletion | Exon 3 of 5 | ENSP00000403682.1 |
Frequencies
GnomAD3 genomes 0.00000893 AC: 1AN: 112006Hom.: 0 Cov.: 24 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
112006
Hom.:
Cov.:
24
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
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Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1066528Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 346804
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1066528
Hom.:
AF XY:
AC XY:
0
AN XY:
346804
African (AFR)
AF:
AC:
0
AN:
25754
American (AMR)
AF:
AC:
0
AN:
30390
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18841
East Asian (EAS)
AF:
AC:
0
AN:
28687
South Asian (SAS)
AF:
AC:
0
AN:
51017
European-Finnish (FIN)
AF:
AC:
0
AN:
38079
Middle Eastern (MID)
AF:
AC:
0
AN:
3135
European-Non Finnish (NFE)
AF:
AC:
0
AN:
825764
Other (OTH)
AF:
AC:
0
AN:
44861
GnomAD4 genome 0.00000893 AC: 1AN: 112006Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34184 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
112006
Hom.:
Cov.:
24
AF XY:
AC XY:
0
AN XY:
34184
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30823
American (AMR)
AF:
AC:
0
AN:
10656
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2641
East Asian (EAS)
AF:
AC:
0
AN:
3547
South Asian (SAS)
AF:
AC:
0
AN:
2688
European-Finnish (FIN)
AF:
AC:
0
AN:
6119
Middle Eastern (MID)
AF:
AC:
0
AN:
238
European-Non Finnish (NFE)
AF:
AC:
1
AN:
53102
Other (OTH)
AF:
AC:
0
AN:
1510
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
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0
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0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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Age
Alfa
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Bravo
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ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:reviewed by expert panel
Pathogenic
VUS
Benign
Condition
6
-
-
Creatine transporter deficiency (9)
2
-
-
not provided (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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