Variant rs151335200 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000253122.10(SLC6A8):c.1515C>A(p.Asp505Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 110,276 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. D505D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Consequence

SLC6A8
ENST00000253122.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.75

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23056585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC6A8	NM_005629.4 linkuse as main transcript	c.1515C>A	p.Asp505Glu	missense_variant	11/13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2 linkuse as main transcript	c.1485C>A	p.Asp495Glu	missense_variant	11/13		NP_001136277.1
SLC6A8	NM_001142806.1 linkuse as main transcript	c.1170C>A	p.Asp390Glu	missense_variant	11/13		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10 linkuse as main transcript	c.1515C>A	p.Asp505Glu	missense_variant	11/13	1	NM_005629.4	ENSP00000253122	P1	P48029-1
SLC6A8	ENST00000430077.6 linkuse as main transcript	c.1170C>A	p.Asp390Glu	missense_variant	11/13	2		ENSP00000403041		P48029-4
SLC6A8	ENST00000413787.1 linkuse as main transcript	c.444C>A	p.Asp148Glu	missense_variant	6/6	5		ENSP00000400463
SLC6A8	ENST00000485324.1 linkuse as main transcript	n.1822C>A		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

AF:

0.00000907

AC:

AN:

110276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32530

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000907

AC:

AN:

110276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32530

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000190

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.070

DANN

Benign

0.97

DEOGEN2

Uncertain

0.42

T;.;.

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

0.86

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Uncertain

0.29

Sift

Benign

0.048

D;T;T

Sift4G

Benign

0.10

T;T;D

Polyphen

0.81

P;.;.

Vest4

0.19

MutPred

0.45

Loss of stability (P = 0.3484);.;.;

MVP

0.60

MPC

0.53

ClinPred

0.49

GERP RS

-8.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over