rs2304725

chr3-10844235-T-Cchr3-10844235-T-G

Variant summary

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

The NM_014229.3(SLC6A11):c.645T>C(p.Ser215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,613,944 control chromosomes in the GnomAD database, including 93,608 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 0.33 (8399 hom., cov: 33)
  • Exomes 𝑓: 0.34 (85209 hom.)
• Consequence: SLC6A11 NM_014229.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.71

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-6.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A11	NM_014229.3	c.645T>C	p.Ser215=	synonymous_variant	5/14	ENST00000254488.7
SLC6A11	XM_047448764.1	c.123T>C	p.Ser41=	synonymous_variant	3/12
SLC6A11	XM_011534033.3	c.645T>C	p.Ser215=	synonymous_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A11	ENST00000254488.7	c.645T>C	p.Ser215=	synonymous_variant	5/14	1	NM_014229.3	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49706 AN: 152040 Hom.: 8394 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.325

GnomAD3 exomes AF: 0.341 AC: 85716 AN: 251176 Hom.: 15921 AF XY: 0.354 AC XY: 48031 AN XY: 135768

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.458

Gnomad SAS exome AF: 0.511

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.337 AC: 492583 AN: 1461786 Hom.: 85209 Cov.: 42 AF XY: 0.343 AC XY: 249412 AN XY: 727198

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.327 AC: 49731 AN: 152158 Hom.: 8399 Cov.: 33 AF XY: 0.329 AC XY: 24506 AN XY: 74388

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.324

Alfa AF: 0.337 Hom.: 23505

Bravo AF: 0.319

Asia WGS AF: 0.456 AC: 1589 AN: 3478

EpiCase AF: 0.344

EpiControl AF: 0.343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.64
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2304725; hg19: chr3-10885920; COSMIC: COSV54391079;