chr3-10935190-A-G

Variant names:

• chr3-10935190-A-G
• rs2245532
• NM_014229.3:c.1737A>G

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.1737A>G​(p.Thr579Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,456 control chromosomes in the GnomAD database, including 128,935 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 0.41 (13633 hom., cov: 33)
  • Exomes 𝑓: 0.39 (115302 hom.)
• Consequence: SLC6A11 NM_014229.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.13
• Publications: 16 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=-0.99).
• BP7: Synonymous conserved (PhyloP=-5.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	NM_014229.3	MANE Select	c.1737A>G	p.Thr579Thr	synonymous	Exon 13 of 14	NP_055044.1	P48066-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.1737A>G	p.Thr579Thr	synonymous	Exon 13 of 14	ENSP00000254488.2	P48066-1
	SLC6A11	ENST00000861594.1		c.1461A>G	p.Thr487Thr	synonymous	Exon 11 of 12	ENSP00000531653.1
	SLC6A11	ENST00000464828.1	TSL:3	n.363A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62746 AN: 152024 Hom.: 13632 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.347 AC: 87079 AN: 250820 AF XY: 0.348

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.480

Gnomad EAS exome AF: 0.0752

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.390 AC: 569375 AN: 1461314 Hom.: 115302 Cov.: 39 AF XY: 0.386 AC XY: 280718 AN XY: 726976

African (AFR) AF: 0.518 AC: 17349 AN: 33472

American (AMR) AF: 0.217 AC: 9688 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 12453 AN: 26112

East Asian (EAS) AF: 0.0890 AC: 3532 AN: 39694

South Asian (SAS) AF: 0.258 AC: 22223 AN: 86228

European-Finnish (FIN) AF: 0.369 AC: 19678 AN: 53398

Middle Eastern (MID) AF: 0.373 AC: 2148 AN: 5766

European-Non Finnish (NFE) AF: 0.413 AC: 459496 AN: 1111566

Other (OTH) AF: 0.378 AC: 22808 AN: 60370

GnomAD4 genome AF: 0.413 AC: 62785 AN: 152142 Hom.: 13633 Cov.: 33 AF XY: 0.403 AC XY: 29978 AN XY: 74372

African (AFR) AF: 0.507 AC: 21056 AN: 41516

American (AMR) AF: 0.305 AC: 4661 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3472

East Asian (EAS) AF: 0.0825 AC: 427 AN: 5174

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3936 AN: 10574

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28616 AN: 67978

Other (OTH) AF: 0.418 AC: 883 AN: 2112

Alfa AF: 0.419 Hom.: 23321

Bravo AF: 0.411

Asia WGS AF: 0.191 AC: 669 AN: 3478

EpiCase AF: 0.415

EpiControl AF: 0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0090
DANN	Benign	0.35
PhyloP100		-5.1
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2245532; hg19: chr3-10976876; COSMIC: COSV54390692;