Genetic Variant NM_005629.4:c.-6G>A (chrX-153688569-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005629.4(SLC6A8):c.-6G>A 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene SLC6A8 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

SLC6A8
NM_005629.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

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

Specifications for SLC6A8 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BS2

High Hemizygotes in GnomAdExome4 at 2 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.-6G>A		5_prime_UTR	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.-6G>A		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.-6G>A	5_prime_UTR	Exon 1 of 13	ENSP00000253122.5	P48029-1
SLC6A8	ENST00000955775.1		c.-6G>A	5_prime_UTR	Exon 1 of 13	ENSP00000625834.1
SLC6A8	ENST00000922630.1		c.-6G>A	5_prime_UTR	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes

AF:

0.0000195

AC:

AN:

102672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000697

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

AF:

0.0000111

AC:

AN:

899392

Hom.:

Cov.:

AF XY:

0.00000721

AC XY:

AN XY:

277510

show subpopulations

African (AFR)

AF:

0.0000553

AC:

AN:

18076

American (AMR)

AF:

0.00

AC:

AN:

14861

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13804

East Asian (EAS)

AF:

0.00

AC:

AN:

16517

South Asian (SAS)

AF:

0.00

AC:

AN:

37607

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2263

European-Non Finnish (NFE)

AF:

0.0000123

AC:

AN:

732646

Other (OTH)

AF:

0.00

AC:

AN:

35404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000195

AC:

AN:

102672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27774

show subpopulations

African (AFR)

AF:

0.0000697

AC:

AN:

28681

American (AMR)

AF:

0.00

AC:

AN:

10020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2521

East Asian (EAS)

AF:

0.00

AC:

AN:

3109

South Asian (SAS)

AF:

0.00

AC:

AN:

2397

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

49659

Other (OTH)

AF:

0.00

AC:

AN:

1395

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.24

PromoterAI

0.015

Neutral

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over