NM_005629.4:c.55_57delAAG

Variant names:

• chrX-153688623-GAGA-G
• rs1603212916
• NM_005629.4:c.55_57delAAG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM1 PM4_Supporting BP6_Moderate

The NM_005629.4(SLC6A8):​c.55_57delAAG​(p.Lys19del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A8 NM_005629.4 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 4 benign, 7 uncertain in NM_005629.4
• PM4: Nonframeshift variant in NON repetitive region in NM_005629.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant X-153688623-GAGA-G is Benign according to our data. Variant chrX-153688623-GAGA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 807837.Status of the report is criteria_provided_single_submitter, 1 stars.

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.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.55_57delAAG	p.Lys19del	conservative_inframe_deletion	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.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000103 AC: 1 AN: 968266 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 309128

African (AFR) AF: 0.00 AC: 0 AN: 19935

American (AMR) AF: 0.00 AC: 0 AN: 19679

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15803

East Asian (EAS) AF: 0.00 AC: 0 AN: 19418

South Asian (SAS) AF: 0.00 AC: 0 AN: 43676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33809

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2592

European-Non Finnish (NFE) AF: 0.00000129 AC: 1 AN: 773940

Other (OTH) AF: 0.00 AC: 0 AN: 39414

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=79/21	polymorphism

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

dbSNP: rs1603212916; hg19: chrX-152954078;