rs376073223

Variant names:

• chrX-153694714-C-G
• rs376073223
• NM_005629.4:c.1597-5C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-153694714-C-G
• chrX-153694714-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005629.4(SLC6A8):​c.1597-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,732 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SLC6A8 NM_005629.4 splice_region, intron
• Scores: Splicing: ADA: 0.003424
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A8	NM_005629.4	c.1597-5C>G		splice_region_variant, intron_variant	Intron 11 of 12	ENST00000253122.10	NP_005620.1
SLC6A8	NM_001142805.2	c.1567-5C>G		splice_region_variant, intron_variant	Intron 11 of 12		NP_001136277.1
SLC6A8	NM_001142806.1	c.1252-5C>G		splice_region_variant, intron_variant	Intron 11 of 12		NP_001136278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1597-5C>G		splice_region_variant, intron_variant	Intron 11 of 12	1	NM_005629.4	ENSP00000253122.5
SLC6A8	ENST00000430077.6	c.1252-5C>G		splice_region_variant, intron_variant	Intron 11 of 12	2		ENSP00000403041.2
SLC6A8	ENST00000485324.1	n.1904-5C>G		splice_region_variant, intron_variant	Intron 4 of 5	2
SLC6A8	ENST00000413787.1	c.*138C>G		downstream_gene_variant		5		ENSP00000400463.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096732 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 362796

African (AFR) AF: 0.00 AC: 0 AN: 26360

American (AMR) AF: 0.00 AC: 0 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40337

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3374

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841783

Other (OTH) AF: 0.00 AC: 0 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	-0.84
CADD	Benign	0.32
DANN	Benign	0.39
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0034
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.060		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: rs376073223; hg19: chrX-152960169;