rs782517934

Variant names:

• chrX-153693325-A-C
• rs782517934
• NM_005629.4:c.975A>C
• SLC6A8 p.Thr325Thr

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_005629.4(SLC6A8):​c.975A>C​(p.Thr325Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000612 in 1,209,647 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). The gene SLC6A8 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000064 (0 hom. 23 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.49
• 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]

SLC6A8 Gene-Disease associations (from GenCC):

• creatine transporter deficiency

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

ACMG classification

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.078).
• BP6: Variant X-153693325-A-C is Benign according to our data. Variant chrX-153693325-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 23 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.975A>C	p.Thr325Thr	synonymous	Exon 6 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.975A>C	p.Thr325Thr	synonymous	Exon 6 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.630A>C	p.Thr210Thr	synonymous	Exon 6 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.975A>C	p.Thr325Thr	synonymous	Exon 6 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.975A>C	p.Thr325Thr	synonymous	Exon 6 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.975A>C	p.Thr325Thr	synonymous	Exon 6 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.0000357 AC: 4 AN: 112161 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000936

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: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000131 AC: 24 AN: 182997 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000219

Gnomad ASJ exome AF: 0.000669

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000147

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.0000638 AC: 70 AN: 1097433 Hom.: 0 Cov.: 32 AF XY: 0.0000634 AC XY: 23 AN XY: 362831

African (AFR) AF: 0.000114 AC: 3 AN: 26387

American (AMR) AF: 0.000170 AC: 6 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.000671 AC: 13 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54125

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40451

Middle Eastern (MID) AF: 0.00145 AC: 6 AN: 4130

European-Non Finnish (NFE) AF: 0.0000428 AC: 36 AN: 841484

Other (OTH) AF: 0.000130 AC: 6 AN: 46067

GnomAD4 genome AF: 0.0000356 AC: 4 AN: 112214 Hom.: 0 Cov.: 24 AF XY: 0.0000291 AC XY: 1 AN XY: 34422

African (AFR) AF: 0.00 AC: 0 AN: 30903

American (AMR) AF: 0.0000935 AC: 1 AN: 10697

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6163

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53092

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000718

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.67
FATHMM_MKL	Benign	0.22	N
PhyloP100		-5.5
PromoterAI		0.036	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs782517934;

hg19: chrX-152958780;