rs371905179

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005629.4(SLC6A8):​c.1016+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000864 in 1,204,237 control chromosomes in the GnomAD database, including 1 homozygotes. There are 58 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 0.000071 ( 0 hom., 5 hem., cov: 24)
Exomes 𝑓: 0.000088 ( 1 hom. 53 hem. )

Consequence

SLC6A8
NM_005629.4 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -7.76
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 -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant X-153693376-G-A is Benign according to our data. Variant chrX-153693376-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 380461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A8NM_005629.4 linkuse as main transcriptc.1016+10G>A intron_variant ENST00000253122.10 NP_005620.1 P48029-1X5D9C4
SLC6A8NM_001142805.2 linkuse as main transcriptc.1016+10G>A intron_variant NP_001136277.1 P48029Q59EV7
SLC6A8NM_001142806.1 linkuse as main transcriptc.671+10G>A intron_variant NP_001136278.1 P48029-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A8ENST00000253122.10 linkuse as main transcriptc.1016+10G>A intron_variant 1 NM_005629.4 ENSP00000253122.5 P48029-1

Frequencies

GnomAD3 genomes
AF:
0.0000714
AC:
8
AN:
112077
Hom.:
0
Cov.:
24
AF XY:
0.000146
AC XY:
5
AN XY:
34281
show subpopulations
Gnomad AFR
AF:
0.0000326
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000187
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00110
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.000664
GnomAD3 exomes
AF:
0.000175
AC:
32
AN:
182890
Hom.:
0
AF XY:
0.000354
AC XY:
24
AN XY:
67742
show subpopulations
Gnomad AFR exome
AF:
0.000153
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00121
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000245
Gnomad OTH exome
AF:
0.000222
GnomAD4 exome
AF:
0.0000879
AC:
96
AN:
1092160
Hom.:
1
Cov.:
31
AF XY:
0.000148
AC XY:
53
AN XY:
357766
show subpopulations
Gnomad4 AFR exome
AF:
0.0000761
Gnomad4 AMR exome
AF:
0.000256
Gnomad4 ASJ exome
AF:
0.0000517
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00115
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000837
Gnomad4 OTH exome
AF:
0.000196
GnomAD4 genome
AF:
0.0000714
AC:
8
AN:
112077
Hom.:
0
Cov.:
24
AF XY:
0.000146
AC XY:
5
AN XY:
34281
show subpopulations
Gnomad4 AFR
AF:
0.0000326
Gnomad4 AMR
AF:
0.000187
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00110
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.000664
Bravo
AF:
0.0000302

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxFeb 07, 2018This 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. -
Creatine transporter deficiency Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.0020
DANN
Benign
0.51
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs371905179; hg19: chrX-152958831; COSMIC: COSV53472979; COSMIC: COSV53472979; API