rs187400676

Variant names:

• chrX-153693604-G-A
• rs187400676
• NM_005629.4:c.1141+18G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005629.4(SLC6A8):​c.1141+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,205,279 control chromosomes in the GnomAD database, including 17 homozygotes. There are 758 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 0.0037 (3 hom., 164 hem., cov: 24)
  • Exomes 𝑓: 0.0018 (14 hom. 594 hem.)
• Consequence: SLC6A8 NM_005629.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.95
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-153693604-G-A is Benign according to our data. Variant chrX-153693604-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 381457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00374 (422/112828) while in subpopulation AMR AF = 0.031 (333/10738). AF 95% confidence interval is 0.0283. There are 3 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.1141+18G>A		intron	N/A	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1111+18G>A		intron	N/A	NP_001136277.1
	SLC6A8	NM_001142806.1		c.796+18G>A		intron	N/A	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.1141+18G>A		intron	N/A	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1141+18G>A		intron	N/A	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1141+18G>A		intron	N/A	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 426 AN: 112775 Hom.: 3 Cov.: 24

Gnomad AFR AF: 0.000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00644

Gnomad SAS AF: 0.000362

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000300

Gnomad OTH AF: 0.00461

GnomAD2 exomes AF: 0.00596 AC: 1088 AN: 182547 AF XY: 0.00476

Gnomad AFR exome AF: 0.000230

Gnomad AMR exome AF: 0.0310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00484

Gnomad FIN exome AF: 0.00675

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00184 AC: 2012 AN: 1092451 Hom.: 14 Cov.: 31 AF XY: 0.00166 AC XY: 594 AN XY: 358591

African (AFR) AF: 0.000228 AC: 6 AN: 26275

American (AMR) AF: 0.0324 AC: 1139 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.0111 AC: 335 AN: 30188

South Asian (SAS) AF: 0.000574 AC: 31 AN: 53983

European-Finnish (FIN) AF: 0.00633 AC: 256 AN: 40423

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3414

European-Non Finnish (NFE) AF: 0.000184 AC: 154 AN: 837766

Other (OTH) AF: 0.00198 AC: 91 AN: 45858

GnomAD4 genome AF: 0.00374 AC: 422 AN: 112828 Hom.: 3 Cov.: 24 AF XY: 0.00469 AC XY: 164 AN XY: 34974

African (AFR) AF: 0.000321 AC: 10 AN: 31154

American (AMR) AF: 0.0310 AC: 333 AN: 10738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00618 AC: 22 AN: 3560

South Asian (SAS) AF: 0.000364 AC: 1 AN: 2751

European-Finnish (FIN) AF: 0.00529 AC: 33 AN: 6233

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000300 AC: 16 AN: 53301

Other (OTH) AF: 0.00455 AC: 7 AN: 1538

Alfa AF: 0.00182 Hom.: 15

Bravo AF: 0.00578

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.70
PhyloP100		-2.0
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs187400676; hg19: chrX-152959059;