Genetic Variant NM_005629.4:c.-11C>T (chrX-153688564-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005629.4(SLC6A8):c.-11C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 4 hem., cov: 18)

Exomes 𝑓: 0.0000068 ( 0 hom. 2 hem. )

Consequence

SLC6A8
NM_005629.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.776

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant X-153688564-C-T is Benign according to our data. Variant chrX-153688564-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 386976.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.-11C>T		5_prime_UTR	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.-11C>T	5_prime_UTR	Exon 1 of 13	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000955775.1		c.-11C>T	5_prime_UTR	Exon 1 of 13	ENSP00000625834.1
SLC6A8	ENST00000922630.1		c.-11C>T	5_prime_UTR	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes

AF:

0.000127

AC:

AN:

102715

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00110

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:

0.0000403

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000725

AC:

AN:

41385

AF XY:

0.0000844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000426

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000681

AC:

AN:

881500

Hom.:

Cov.:

AF XY:

0.00000742

AC XY:

AN XY:

269378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17538

American (AMR)

AF:

0.000296

AC:

AN:

13506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13290

East Asian (EAS)

AF:

0.00

AC:

AN:

16087

South Asian (SAS)

AF:

0.00

AC:

AN:

36116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2185

European-Non Finnish (NFE)

AF:

0.00000277

AC:

AN:

721149

Other (OTH)

AF:

0.00

AC:

AN:

34533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000127

AC:

AN:

102715

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

27879

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28768

American (AMR)

AF:

0.00110

AC:

AN:

10038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2521

East Asian (EAS)

AF:

0.00

AC:

AN:

3112

South Asian (SAS)

AF:

0.00

AC:

AN:

2367

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4067

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.0000403

AC:

AN:

49623

Other (OTH)

AF:

0.00

AC:

AN:

1400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.000110

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.97

PhyloP100

0.78

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Mutation Taster

=300/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over