rs148232368

Variant names:

• chrX-153693043-C-A
• rs148232368
• NM_005629.4:c.780C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153693043-C-A
• chrX-153693043-C-G
• chrX-153693043-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005629.4(SLC6A8):​c.780C>A​(p.Ile260Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,096,827 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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. I260I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000036 (0 hom. 1 hem.)
• Consequence: SLC6A8 NM_005629.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• 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, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.780C>A	p.Ile260Ile	splice_region_variant, synonymous_variant	Exon 5 of 13	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.780C>A	p.Ile260Ile	splice_region_variant, synonymous_variant	Exon 5 of 13		NP_001136277.1
SLC6A8	NM_001142806.1	c.435C>A	p.Ile145Ile	splice_region_variant, synonymous_variant	Exon 5 of 13		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.780C>A	p.Ile260Ile	splice_region_variant, synonymous_variant	Exon 5 of 13	1	NM_005629.4	ENSP00000253122.5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1096827 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 1 AN XY: 362785

African (AFR) AF: 0.00 AC: 0 AN: 26367

American (AMR) AF: 0.00 AC: 0 AN: 35197

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40431

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3380

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841794

Other (OTH) AF: 0.0000217 AC: 1 AN: 45998

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		-0.96
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: 2

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

Other links and lift over

dbSNP: rs148232368; hg19: chrX-152958498;