rs151335200

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005629.4(SLC6A8):​c.1515C>A​(p.Asp505Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 110,276 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Consequence

SLC6A8
NM_005629.4 missense

Scores

7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.75
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23056585).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A8NM_005629.4 linkuse as main transcriptc.1515C>A p.Asp505Glu missense_variant 11/13 ENST00000253122.10 NP_005620.1 P48029-1X5D9C4
SLC6A8NM_001142805.2 linkuse as main transcriptc.1485C>A p.Asp495Glu missense_variant 11/13 NP_001136277.1 P48029Q59EV7
SLC6A8NM_001142806.1 linkuse as main transcriptc.1170C>A p.Asp390Glu missense_variant 11/13 NP_001136278.1 P48029-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A8ENST00000253122.10 linkuse as main transcriptc.1515C>A p.Asp505Glu missense_variant 11/131 NM_005629.4 ENSP00000253122.5 P48029-1
SLC6A8ENST00000430077.6 linkuse as main transcriptc.1170C>A p.Asp390Glu missense_variant 11/132 ENSP00000403041.2 P48029-4
SLC6A8ENST00000413787.1 linkuse as main transcriptc.444C>A p.Asp148Glu missense_variant 6/65 ENSP00000400463.1 H7C1I2
SLC6A8ENST00000485324.1 linkuse as main transcriptn.1822C>A non_coding_transcript_exon_variant 4/62

Frequencies

GnomAD3 genomes
AF:
0.00000907
AC:
1
AN:
110276
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
32530
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000190
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.00000907
AC:
1
AN:
110276
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
32530
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000190
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
0.070
DANN
Benign
0.97
DEOGEN2
Uncertain
0.42
T;.;.
FATHMM_MKL
Benign
0.17
N
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
1.7
L;.;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-2.5
D;D;D
REVEL
Uncertain
0.29
Sift
Benign
0.048
D;T;T
Sift4G
Benign
0.10
T;T;D
Polyphen
0.81
P;.;.
Vest4
0.19
MutPred
0.45
Loss of stability (P = 0.3484);.;.;
MVP
0.60
MPC
0.53
ClinPred
0.49
T
GERP RS
-8.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.32
gMVP
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs151335200; hg19: chrX-152960007; API