Variant rs187400676 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005629.4(SLC6A8):c.1141+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,205,279 control chromosomes in the GnomAD database, including 17 homozygotes. There are 758 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 0.0037 ( 3 hom., 164 hem., cov: 24)

Exomes 𝑓: 0.0018 ( 14 hom. 594 hem. )

Consequence

SLC6A8
NM_005629.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.95

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]

SLC6A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-153693604-G-A is Benign according to our data. Variant chrX-153693604-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 381457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153693604-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00374 (422/112828) while in subpopulation AMR AF= 0.031 (333/10738). AF 95% confidence interval is 0.0283. There are 3 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SLC6A8	NM_005629.4 linkuse as main transcript	c.1141+18G>A	intron_variant	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2 linkuse as main transcript	c.1111+18G>A	intron_variant		NP_001136277.1
SLC6A8	NM_001142806.1 linkuse as main transcript	c.796+18G>A	intron_variant		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.1141+18G>A		intron_variant		1	NM_005629.4	ENSP00000253122	P1	P48029-1

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

426

AN:

112775

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

164

AN XY:

34911

show subpopulations

Gnomad AFR

AF:

0.000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00644

Gnomad SAS

AF:

0.000362

Gnomad FIN

AF:

0.00529

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.00461

GnomAD3 exomes

AF:

0.00596

AC:

1088

AN:

182547

Hom.:

AF XY:

0.00476

AC XY:

321

AN XY:

67487

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00484

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.00675

Gnomad NFE exome

AF:

0.000382

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00184

AC:

2012

AN:

1092451

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

594

AN XY:

358591

show subpopulations

Gnomad4 AFR exome

AF:

0.000228

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0111

Gnomad4 SAS exome

AF:

0.000574

Gnomad4 FIN exome

AF:

0.00633

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00198

GnomAD4 genome

AF:

0.00374

AC:

422

AN:

112828

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

164

AN XY:

34974

show subpopulations

Gnomad4 AFR

AF:

0.000321

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00618

Gnomad4 SAS

AF:

0.000364

Gnomad4 FIN

AF:

0.00529

Gnomad4 NFE

AF:

0.000300

Gnomad4 OTH

AF:

0.00455

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.00578

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2016

This 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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.15

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over