rs782627741

chrX-153693909-G-AchrX-153693909-G-CchrX-153693909-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_005629.4(SLC6A8):c.1146G>A(p.Pro382=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,045,851 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P382P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000036 (0 hom. 14 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.20

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19111669).
• BP6: Variant X-153693909-G-A is Benign according to our data. Variant chrX-153693909-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A8	NM_005629.4	c.1146G>A	p.Pro382=	synonymous_variant	8/13	ENST00000253122.10
SLC6A8	NM_001142805.2	c.1116G>A	p.Pro372=	synonymous_variant	8/13
SLC6A8	NM_001142806.1	c.801G>A	p.Pro267=	synonymous_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A8	ENST00000253122.10	c.1146G>A	p.Pro382=	synonymous_variant	8/13	1	NM_005629.4	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000434 AC: 5 AN: 115313 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40283

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000698

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 38 AN: 1045851 Hom.: 0 Cov.: 31 AF XY: 0.0000415 AC XY: 14 AN XY: 337635

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000178

Gnomad4 ASJ exome AF: 0.0000538

Gnomad4 EAS exome AF: 0.0000366

Gnomad4 SAS exome AF: 0.000181

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000264

ExAC AF: 0.0000101 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Creatine transporter deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.5
Dann	Benign	0.82
FATHMM_MKL	Benign	0.18	N
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.053
MutPred		0.24		Gain of methylation at G44 (P = 0.009);
MVP		0.50
ClinPred		0.72	D
GERP RS		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs782627741; hg19: chrX-152959364;