Variant X-153694749-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate

The NM_005629.4(SLC6A8):c.1627G>C(p.Glu543Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E543K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

SLC6A8
NM_005629.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.537

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant X-153694749-G-C is Benign according to our data. Variant chrX-153694749-G-C is described in ClinVar as [Benign]. Clinvar id is 1169766.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC6A8	NM_005629.4 linkuse as main transcript	c.1627G>C	p.Glu543Gln	missense_variant	12/13	ENST00000253122.10
SLC6A8	NM_001142805.2 linkuse as main transcript	c.1597G>C	p.Glu533Gln	missense_variant	12/13
SLC6A8	NM_001142806.1 linkuse as main transcript	c.1282G>C	p.Glu428Gln	missense_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.1627G>C	p.Glu543Gln	missense_variant	12/13	1	NM_005629.4	P1	P48029-1
SLC6A8	ENST00000430077.6 linkuse as main transcript	c.1282G>C	p.Glu428Gln	missense_variant	12/13	2			P48029-4
SLC6A8	ENST00000485324.1 linkuse as main transcript	n.1934G>C		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182609

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67637

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000273

AC:

AN:

1097214

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Creatine transporter deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.0

DANN

Benign

0.58

DEOGEN2

Benign

0.10

T;.

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.010

N;.

MutationTaster

Benign

0.61

D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.13

Sift

Benign

0.22

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.012

B;.

Vest4

0.057

MutPred

0.37

Loss of sheet (P = 0.1907);.;

MVP

0.39

MPC

0.16

ClinPred

0.057

GERP RS

-6.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.58

Position offset: 3

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