rs2272400

Positions:

• chr3-10934163-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014229.3(SLC6A11):​c.1572C>T​(p.Cys524=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,608,836 control chromosomes in the GnomAD database, including 944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (83 hom., cov: 32)
  • Exomes 𝑓: 0.015 (861 hom.)
• Consequence: SLC6A11 NM_014229.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

Genes affected

SLC6A11 (HGNC:11044): (solute carrier family 6 member 11) The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.457 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A11	NM_014229.3	c.1572C>T	p.Cys524=	synonymous_variant	12/14	ENST00000254488.7
SLC6A11	XM_047448764.1	c.1050C>T	p.Cys350=	synonymous_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A11	ENST00000254488.7	c.1572C>T	p.Cys524=	synonymous_variant	12/14	1	NM_014229.3	P1
	ENST00000656787.1	n.350+2827G>A		intron_variant, non_coding_transcript_variant
SLC6A11	ENST00000464828.1	n.198C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2315 AN: 152132 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00915

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.00914

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00770

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0258 AC: 6472 AN: 251082 Hom.: 333 AF XY: 0.0264 AC XY: 3580 AN XY: 135704

Gnomad AFR exome AF: 0.00867

Gnomad AMR exome AF: 0.00819

Gnomad ASJ exome AF: 0.00814

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.0563

Gnomad FIN exome AF: 0.00828

Gnomad NFE exome AF: 0.00726

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0148 AC: 21548 AN: 1456586 Hom.: 861 Cov.: 29 AF XY: 0.0161 AC XY: 11650 AN XY: 725008

Gnomad4 AFR exome AF: 0.00731

Gnomad4 AMR exome AF: 0.00767

Gnomad4 ASJ exome AF: 0.00897

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.0564

Gnomad4 FIN exome AF: 0.00877

Gnomad4 NFE exome AF: 0.00653

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0151 AC: 2306 AN: 152250 Hom.: 83 Cov.: 32 AF XY: 0.0169 AC XY: 1257 AN XY: 74436

Gnomad4 AFR AF: 0.00917

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.00914

Gnomad4 NFE AF: 0.00771

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00991 Hom.: 70

Bravo AF: 0.0147

Asia WGS AF: 0.120 AC: 417 AN: 3478

EpiCase AF: 0.00710

EpiControl AF: 0.00729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.3
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2272400; hg19: chr3-10975849; COSMIC: COSV54397103;