X-153688613-G-A

Variant names:

• chrX-153688613-G-A
• NM_005629.4:c.39G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005629.4(SLC6A8):​c.39G>A​(p.Val13Val) variant causes a synonymous 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: not found (cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.283
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-153688613-G-A is Benign according to our data. Variant chrX-153688613-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1107071.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.283 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.39G>A	p.Val13Val	synonymous	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.39G>A	p.Val13Val	synonymous	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.39G>A	p.Val13Val	synonymous	Exon 1 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.39G>A	p.Val13Val	synonymous	Exon 1 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.39G>A	p.Val13Val	synonymous	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 967156 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 309470

African (AFR) AF: 0.00 AC: 0 AN: 19839

American (AMR) AF: 0.00 AC: 0 AN: 19369

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15699

East Asian (EAS) AF: 0.00 AC: 0 AN: 19255

South Asian (SAS) AF: 0.00 AC: 0 AN: 43565

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 774068

Other (OTH) AF: 0.00 AC: 0 AN: 39283

GnomAD4 genome Cov.: 20

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.99
PhyloP100		0.28
PromoterAI		0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

hg19: chrX-152954068;