rs144252036

Variant names:

• chrX-153693465-C-T
• rs144252036
• NM_005629.4:c.1020C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005629.4(SLC6A8):​c.1020C>T​(p.Asp340Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000736 in 1,209,311 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 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 0.00022 (0 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 0.000058 (0 hom. 17 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.55
• 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: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07809362).
• BP6: Variant X-153693465-C-T is Benign according to our data. Variant chrX-153693465-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 379434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 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.1020C>T	p.Asp340Asp	synonymous	Exon 7 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142806.1		c.675C>T	p.Asp225Asp	synonymous	Exon 7 of 13	NP_001136278.1	P48029-4
	SLC6A8	NM_001142805.2		c.1017-27C>T		intron	N/A	NP_001136277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.1020C>T	p.Asp340Asp	synonymous	Exon 7 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000457723.1	TSL:5	c.4C>T	p.Arg2Cys	missense	Exon 1 of 3	ENSP00000394742.1	H7C0F5
	SLC6A8	ENST00000955775.1		c.1020C>T	p.Asp340Asp	synonymous	Exon 7 of 13	ENSP00000625834.1

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 25 AN: 111684 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000125 AC: 23 AN: 183363 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00106

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000583 AC: 64 AN: 1097577 Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 17 AN XY: 362975

African (AFR) AF: 0.00110 AC: 29 AN: 26390

American (AMR) AF: 0.000142 AC: 5 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4113

European-Non Finnish (NFE) AF: 0.0000309 AC: 26 AN: 841568

Other (OTH) AF: 0.00 AC: 0 AN: 46062

GnomAD4 genome AF: 0.000224 AC: 25 AN: 111734 Hom.: 0 Cov.: 24 AF XY: 0.000118 AC XY: 4 AN XY: 33912

African (AFR) AF: 0.000780 AC: 24 AN: 30787

American (AMR) AF: 0.00 AC: 0 AN: 10570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2649

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53051

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000310

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	1.0
DANN	Benign	0.79
FATHMM_MKL	Benign	0.37	N
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.37	T
PhyloP100		-1.6
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.20
Sift4G	Uncertain	0.014	D
MVP		0.79
ClinPred		0.12	T
GERP RS		-4.4
PromoterAI		-0.094	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs144252036; hg19: chrX-152958920;