rs782433720

Variant names:

• chrX-153691561-C-A
• rs782433720
• NM_005629.4:c.644+8C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153691561-C-A
• chrX-153691561-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005629.4(SLC6A8):​c.644+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: SLC6A8 NM_005629.4 splice_region, intron
• Scores: Splicing: ADA: 0.005852
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.339
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant X-153691561-C-A is Benign according to our data. Variant chrX-153691561-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1632939.Status of the report is criteria_provided_single_submitter, 1 stars.

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.644+8C>A		splice_region intron	N/A	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.644+8C>A		splice_region intron	N/A	NP_001136277.1
	SLC6A8	NM_001142806.1		c.299+8C>A		splice_region 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.644+8C>A		splice_region intron	N/A	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.644+8C>A		splice_region intron	N/A	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.644+8C>A		splice_region intron	N/A	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Creatine transporter deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.7
DANN	Benign	0.81
PhyloP100		0.34
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0059
dbscSNV1_RF	Benign	0.18
SpliceAI score (max)		0.010		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: rs782433720; hg19: chrX-152957016; COSMIC: COSV53472853; COSMIC: COSV53472853;