dbSNP rs144252036: SLC6A8:p.Asp340Asp (chrX-153693465-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005629.4(SLC6A8):c.1020C>T(p.Asp340Asp) 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
NM_005629.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.55

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

creatine transporter deficiency
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

SLC6A8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC6A8	NM_005629.4	MANE Select	c.1020C>T	p.Asp340Asp	synonymous	Exon 7 of 13	NP_005620.1
SLC6A8	NM_001142806.1		c.675C>T	p.Asp225Asp	synonymous	Exon 7 of 13	NP_001136278.1
SLC6A8	NM_001142805.2		c.1017-27C>T		intron	N/A	NP_001136277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.1020C>T	p.Asp340Asp	synonymous	Exon 7 of 13	ENSP00000253122.5
SLC6A8	ENST00000457723.1	TSL:5	c.4C>T	p.Arg2Cys	missense	Exon 1 of 3	ENSP00000394742.1
SLC6A8	ENST00000430077.6	TSL:2	c.675C>T	p.Asp225Asp	synonymous	Exon 7 of 13	ENSP00000403041.2

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

111684

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000125

AC:

AN:

183363

AF XY:

0.0000884

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000583

AC:

AN:

1097577

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

362975

show subpopulations

African (AFR)

AF:

0.00110

AC:

AN:

26390

American (AMR)

AF:

0.000142

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.0000554

AC:

AN:

54132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40526

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4113

European-Non Finnish (NFE)

AF:

0.0000309

AC:

AN:

841568

Other (OTH)

AF:

0.00

AC:

AN:

46062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000224

AC:

AN:

111734

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33912

show subpopulations

African (AFR)

AF:

0.000780

AC:

AN:

30787

American (AMR)

AF:

0.00

AC:

AN:

10570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.00

AC:

AN:

2649

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53051

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

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

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

May 02, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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

May 25, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

1.0

(source)

DANN

Benign

0.79

FATHMM_MKL

Benign

0.37

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.37

PhyloP100

-1.6

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.20

Sift4G

Uncertain

0.014

MVP

0.79

ClinPred

0.12

GERP RS

-4.4

PromoterAI

-0.094

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over