chrX-153695196-G-C

Variant names:

• chrX-153695196-G-C
• rs376385129
• NM_005629.4:c.1890G>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005629.4(SLC6A8):​c.1890G>C​(p.Val630Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,184,274 control chromosomes in the GnomAD database, including 6 homozygotes. There are 51 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 0.00019 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00018 (6 hom. 45 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.80
• Publications: 1 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]

SLC6A8 Gene-Disease associations (from GenCC):

• creatine transporter deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-153695196-G-C is Benign according to our data. Variant chrX-153695196-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 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.1890G>C	p.Val630Val	synonymous	Exon 13 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1860G>C	p.Val620Val	synonymous	Exon 13 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1545G>C	p.Val515Val	synonymous	Exon 13 of 13	NP_001136278.1	P48029-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.1890G>C	p.Val630Val	synonymous	Exon 13 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1887G>C	p.Val629Val	synonymous	Exon 13 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1881G>C	p.Val627Val	synonymous	Exon 13 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.000189 AC: 21 AN: 111307 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000285

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00310

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

GnomAD2 exomes AF: 0.000191 AC: 27 AN: 141510 AF XY: 0.000113

Gnomad AFR exome AF: 0.000420

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00119

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.000184 AC: 197 AN: 1072914 Hom.: 6 Cov.: 31 AF XY: 0.000129 AC XY: 45 AN XY: 348874

African (AFR) AF: 0.000117 AC: 3 AN: 25736

American (AMR) AF: 0.0000927 AC: 3 AN: 32377

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18985

East Asian (EAS) AF: 0.00139 AC: 40 AN: 28717

South Asian (SAS) AF: 0.0000391 AC: 2 AN: 51182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38299

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3823

European-Non Finnish (NFE) AF: 0.0000109 AC: 9 AN: 828675

Other (OTH) AF: 0.00310 AC: 140 AN: 45120

GnomAD4 genome AF: 0.000189 AC: 21 AN: 111360 Hom.: 0 Cov.: 23 AF XY: 0.000179 AC XY: 6 AN XY: 33564

African (AFR) AF: 0.000229 AC: 7 AN: 30630

American (AMR) AF: 0.000284 AC: 3 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00311 AC: 11 AN: 3534

South Asian (SAS) AF: 0.00 AC: 0 AN: 2614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52945

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.000283

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Creatine transporter deficiency (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	SLC6A8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs376385129; hg19: chrX-152960651;