Variant rs1181103233 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005629.4(SLC6A8):c.1874G>A(p.Ser625Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000504 in 1,190,973 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000054 ( 0 hom. 22 hem. )

Consequence

SLC6A8
NM_005629.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 5.18

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:

SLC6A8 (HGNC:):

SLC6A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09410134).

BS2

High Hemizygotes in GnomAdExome4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A8	NM_005629.4 linkuse as main transcript	c.1874G>A	p.Ser625Asn	missense_variant	13/13	ENST00000253122.10	NP_005620.1	P48029-1X5D9C4
SLC6A8	NM_001142805.2 linkuse as main transcript	c.1844G>A	p.Ser615Asn	missense_variant	13/13		NP_001136277.1	P48029Q59EV7
SLC6A8	NM_001142806.1 linkuse as main transcript	c.1529G>A	p.Ser510Asn	missense_variant	13/13		NP_001136278.1	P48029-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.1874G>A	p.Ser625Asn	missense_variant	13/13	1	NM_005629.4	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000430077.6 linkuse as main transcript	c.1529G>A	p.Ser510Asn	missense_variant	13/13	2		ENSP00000403041.2	P48029-4
SLC6A8	ENST00000485324.1 linkuse as main transcript	n.2181G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111621

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33789

show subpopulations

Gnomad AFR

AF:

0.0000326

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149653

Hom.:

AF XY:

0.00

AC XY:

AN XY:

46391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000320

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000537

AC:

AN:

1079352

Hom.:

Cov.:

AF XY:

0.0000627

AC XY:

AN XY:

351154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000386

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000661

Gnomad4 OTH exome

AF:

0.0000441

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111621

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33789

show subpopulations

Gnomad4 AFR

AF:

0.0000326

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2019	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Uncertain significance, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 30, 2018	- -

Creatine deficiency syndrome 1

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.80

T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.16

Sift

Benign

0.45

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0

B;.

Vest4

0.049

MutPred

0.22

Loss of disorder (P = 0.0673);.;

MVP

0.13

MPC

0.14

ClinPred

0.22

GERP RS

5.3

Varity_R

0.16

gMVP

0.49

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