NM_005629.4:c.87G>A

Variant names:

• chrX-153688661-G-A
• rs782373793
• NM_005629.4:c.87G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005629.4(SLC6A8):​c.87G>A​(p.Gly29Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,080,808 control chromosomes in the GnomAD database, including 1 homozygotes. There are 180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G29G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., 13 hem., cov: 20)
  • Exomes 𝑓: 0.00031 (1 hom. 167 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.906
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant X-153688661-G-A is Benign according to our data. Variant chrX-153688661-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.906 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000222 (24/107987) while in subpopulation SAS AF = 0.00781 (20/2561). AF 95% confidence interval is 0.00518. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 13 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.87G>A	p.Gly29Gly	synonymous	Exon 1 of 13	NP_005620.1
	SLC6A8	NM_001142805.2		c.87G>A	p.Gly29Gly	synonymous	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.87G>A	p.Gly29Gly	synonymous	Exon 1 of 13	ENSP00000253122.5
	PNCK	ENST00000458354.5	TSL:3	c.-3+154C>T		intron	N/A	ENSP00000401542.1
	PNCK	ENST00000480693.1	TSL:5	n.64+154C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000222 AC: 24 AN: 107973 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000995

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00777

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000195

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000982 AC: 60 AN: 61074 AF XY: 0.00214

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000312 AC: 304 AN: 972821 Hom.: 1 Cov.: 26 AF XY: 0.000537 AC XY: 167 AN XY: 310985

African (AFR) AF: 0.00 AC: 0 AN: 20012

American (AMR) AF: 0.00 AC: 0 AN: 19082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15870

East Asian (EAS) AF: 0.00 AC: 0 AN: 19999

South Asian (SAS) AF: 0.00668 AC: 289 AN: 43262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2746

European-Non Finnish (NFE) AF: 0.00000386 AC: 3 AN: 778007

Other (OTH) AF: 0.000302 AC: 12 AN: 39701

GnomAD4 genome AF: 0.000222 AC: 24 AN: 107987 Hom.: 0 Cov.: 20 AF XY: 0.000414 AC XY: 13 AN XY: 31393

African (AFR) AF: 0.0000993 AC: 3 AN: 30204

American (AMR) AF: 0.00 AC: 0 AN: 10521

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2589

East Asian (EAS) AF: 0.00 AC: 0 AN: 3277

South Asian (SAS) AF: 0.00781 AC: 20 AN: 2561

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5179

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 202

European-Non Finnish (NFE) AF: 0.0000195 AC: 1 AN: 51338

Other (OTH) AF: 0.00 AC: 0 AN: 1483

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Creatine transporter deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		-0.91
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs782373793; hg19: chrX-152954116;