3-10934163-C-T

Variant names:

• chr3-10934163-C-T
• rs2272400
• NM_014229.3:c.1572C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014229.3(SLC6A11):​c.1572C>T​(p.Cys524Cys) 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
• Publications: 14 publications found

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]

ENSG00000286962 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014229.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	NM_014229.3	MANE Select	c.1572C>T	p.Cys524Cys	synonymous	Exon 12 of 14	NP_055044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.1572C>T	p.Cys524Cys	synonymous	Exon 12 of 14	ENSP00000254488.2
	SLC6A11	ENST00000464828.1	TSL:3	n.198C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000286962	ENST00000656787.1		n.350+2827G>A		intron	N/A

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

GnomAD2 exomes AF: 0.0258 AC: 6472 AN: 251082 AF XY: 0.0264

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 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

African (AFR) AF: 0.00731 AC: 244 AN: 33382

American (AMR) AF: 0.00767 AC: 343 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00897 AC: 234 AN: 26100

East Asian (EAS) AF: 0.176 AC: 6984 AN: 39652

South Asian (SAS) AF: 0.0564 AC: 4854 AN: 86098

European-Finnish (FIN) AF: 0.00877 AC: 468 AN: 53390

Middle Eastern (MID) AF: 0.00886 AC: 51 AN: 5756

European-Non Finnish (NFE) AF: 0.00653 AC: 7230 AN: 1107288

Other (OTH) AF: 0.0189 AC: 1140 AN: 60210

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

African (AFR) AF: 0.00917 AC: 381 AN: 41546

American (AMR) AF: 0.00667 AC: 102 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.162 AC: 839 AN: 5174

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4824

European-Finnish (FIN) AF: 0.00914 AC: 97 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00771 AC: 524 AN: 68004

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0104 Hom.: 107

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.3
DANN	Benign	0.78
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272400; hg19: chr3-10975849; COSMIC: COSV54397103;