rs144252036

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000253122.10(SLC6A8):​c.1020C>T​(p.Asp340=) 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
ENST00000253122.10 synonymous

Scores

1
1
8

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.55
Variant links:
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]

Genome browser will be placed here

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
SLC6A8NM_005629.4 linkuse as main transcriptc.1020C>T p.Asp340= synonymous_variant 7/13 ENST00000253122.10 NP_005620.1
SLC6A8NM_001142806.1 linkuse as main transcriptc.675C>T p.Asp225= synonymous_variant 7/13 NP_001136278.1
SLC6A8NM_001142805.2 linkuse as main transcriptc.1017-27C>T intron_variant NP_001136277.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A8ENST00000253122.10 linkuse as main transcriptc.1020C>T p.Asp340= synonymous_variant 7/131 NM_005629.4 ENSP00000253122 P1P48029-1

Frequencies

GnomAD3 genomes
AF:
0.000224
AC:
25
AN:
111684
Hom.:
0
Cov.:
24
AF XY:
0.000118
AC XY:
4
AN XY:
33852
show subpopulations
Gnomad AFR
AF:
0.000781
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000125
AC:
23
AN:
183363
Hom.:
0
AF XY:
0.0000884
AC XY:
6
AN XY:
67881
show subpopulations
Gnomad AFR exome
AF:
0.00106
Gnomad AMR exome
AF:
0.0000729
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.000157
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000244
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000583
AC:
64
AN:
1097577
Hom.:
0
Cov.:
32
AF XY:
0.0000468
AC XY:
17
AN XY:
362975
show subpopulations
Gnomad4 AFR exome
AF:
0.00110
Gnomad4 AMR exome
AF:
0.000142
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000554
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000309
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000224
AC:
25
AN:
111734
Hom.:
0
Cov.:
24
AF XY:
0.000118
AC XY:
4
AN XY:
33912
show subpopulations
Gnomad4 AFR
AF:
0.000780
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000285
Hom.:
0
Bravo
AF:
0.000310
ESP6500AA
AF:
0.00104
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 02, 2019This 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 submitterclinical testingGeneDxMay 25, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
1.0
DANN
Benign
0.79
FATHMM_MKL
Benign
0.37
N
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.37
T
MutationTaster
Benign
1.0
D;D
PROVEAN
Pathogenic
-8.0
D
REVEL
Benign
0.20
Sift4G
Uncertain
0.014
D
MVP
0.79
ClinPred
0.12
T
GERP RS
-4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144252036; hg19: chrX-152958920; API