dbSNP rs782197450: SLC6A8:p.Pro31Pro (chrX-153688667-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005629.4(SLC6A8):c.93G>A(p.Pro31Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000926 in 107,995 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000093 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SLC6A8
NM_005629.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.498

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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-153688667-G-A is Benign according to our data. Variant chrX-153688667-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 465149.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.498 with no splicing effect.

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.93G>A	p.Pro31Pro	synonymous	Exon 1 of 13	NP_005620.1
	SLC6A8	NM_001142805.2		c.93G>A	p.Pro31Pro	synonymous	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.93G>A	p.Pro31Pro	synonymous	Exon 1 of 13	ENSP00000253122.5
SLC6A8	ENST00000955775.1		c.93G>A	p.Pro31Pro	synonymous	Exon 1 of 13	ENSP00000625834.1
SLC6A8	ENST00000922630.1		c.93G>A	p.Pro31Pro	synonymous	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes

AF:

0.00000926

AC:

AN:

107995

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000331

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

973799

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

310965

African (AFR)

AF:

0.00

AC:

AN:

20076

American (AMR)

AF:

0.00

AC:

AN:

19245

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15858

East Asian (EAS)

AF:

0.00

AC:

AN:

20049

South Asian (SAS)

AF:

0.00

AC:

AN:

43391

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2794

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

778369

Other (OTH)

AF:

0.00

AC:

AN:

39769

GnomAD4 genome

AF:

0.00000926

AC:

AN:

107995

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

31441

show subpopulations

African (AFR)

AF:

0.0000331

AC:

AN:

30179

American (AMR)

AF:

0.00

AC:

AN:

10506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2586

East Asian (EAS)

AF:

0.00

AC:

AN:

3294

South Asian (SAS)

AF:

0.00

AC:

AN:

2579

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5193

Middle Eastern (MID)

AF:

0.00

AC:

AN:

221

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51337

Other (OTH)

AF:

0.00

AC:

AN:

1468

Age Distribution

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Creatine transporter deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

-0.50

PromoterAI

0.0036

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

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

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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