Genetic Variant NM_005629.4:c.8A>G (chrX-153688582-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005629.4(SLC6A8):c.8A>G(p.Lys3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K3E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.0000011 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

SLC6A8
NM_005629.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.937

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 links:

PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

PNCK links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16235435).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.8A>G	p.Lys3Arg	missense	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.8A>G	p.Lys3Arg	missense	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.8A>G	p.Lys3Arg	missense	Exon 1 of 13	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000955775.1		c.8A>G	p.Lys3Arg	missense	Exon 1 of 13	ENSP00000625834.1
SLC6A8	ENST00000922630.1		c.8A>G	p.Lys3Arg	missense	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000109

AC:

AN:

921450

Hom.:

Cov.:

AF XY:

0.00000348

AC XY:

AN XY:

287438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18732

American (AMR)

AF:

0.00

AC:

AN:

16710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14331

East Asian (EAS)

AF:

0.0000586

AC:

AN:

17062

South Asian (SAS)

AF:

0.00

AC:

AN:

39872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29949

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2359

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

745939

Other (OTH)

AF:

0.00

AC:

AN:

36496

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.097

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

0.94

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.25

REVEL

Benign

0.17

Sift

Benign

0.17

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.076

MutPred

0.15

Loss of ubiquitination at K3 (P = 0.0134)

MVP

0.26

MPC

1.0

ClinPred

0.28

GERP RS

2.6

PromoterAI

-0.034

Neutral

(source)

Varity_R

0.13

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over