chrX-153695196-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005629.4(SLC6A8):​c.1890G>A​(p.Val630Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 111,307 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V630V) has been classified as Likely benign. The gene SLC6A8 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.

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>A	p.Val630Val	synonymous	Exon 13 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.1860G>A	p.Val620Val	synonymous	Exon 13 of 13	NP_001136277.1
	SLC6A8	NM_001142806.1		c.1545G>A	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>A	p.Val630Val	synonymous	Exon 13 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.1887G>A	p.Val629Val	synonymous	Exon 13 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.1881G>A	p.Val627Val	synonymous	Exon 13 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111307 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000327

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.32e-7 AC: 1 AN: 1072915 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 348875

African (AFR) AF: 0.00 AC: 0 AN: 25736

American (AMR) AF: 0.00 AC: 0 AN: 32377

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 28717

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00000121 AC: 1 AN: 828676

Other (OTH) AF: 0.00 AC: 0 AN: 45120

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111307 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33501

African (AFR) AF: 0.0000327 AC: 1 AN: 30562

American (AMR) AF: 0.00 AC: 0 AN: 10533

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.00 AC: 0 AN: 2622

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52952

Other (OTH) AF: 0.00 AC: 0 AN: 1488

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;