3-10934059-C-T

Variant names:

• chr3-10934059-C-T
• rs2272399
• NM_014229.3:c.1475-7C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014229.3(SLC6A11):​c.1475-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,604,318 control chromosomes in the GnomAD database, including 87,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7443 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80034 hom.)
• Consequence: SLC6A11 NM_014229.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003183
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 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.1475-7C>T		splice_region intron	N/A	NP_055044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.1475-7C>T		splice_region intron	N/A	ENSP00000254488.2
	SLC6A11	ENST00000464828.1	TSL:3	n.94C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000286962	ENST00000656787.1		n.350+2931G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46328 AN: 151902 Hom.: 7447 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.316

GnomAD2 exomes AF: 0.334 AC: 83781 AN: 250736 AF XY: 0.342

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.593

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.326 AC: 473805 AN: 1452298 Hom.: 80034 Cov.: 28 AF XY: 0.330 AC XY: 238465 AN XY: 723236

African (AFR) AF: 0.229 AC: 7635 AN: 33300

American (AMR) AF: 0.234 AC: 10473 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 9220 AN: 26060

East Asian (EAS) AF: 0.583 AC: 23131 AN: 39644

South Asian (SAS) AF: 0.385 AC: 33088 AN: 85948

European-Finnish (FIN) AF: 0.353 AC: 18831 AN: 53376

Middle Eastern (MID) AF: 0.420 AC: 2414 AN: 5750

European-Non Finnish (NFE) AF: 0.316 AC: 348330 AN: 1103474

Other (OTH) AF: 0.344 AC: 20683 AN: 60052

GnomAD4 genome AF: 0.305 AC: 46351 AN: 152020 Hom.: 7443 Cov.: 32 AF XY: 0.309 AC XY: 22980 AN XY: 74286

African (AFR) AF: 0.232 AC: 9632 AN: 41472

American (AMR) AF: 0.272 AC: 4149 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3470

East Asian (EAS) AF: 0.578 AC: 2987 AN: 5164

South Asian (SAS) AF: 0.400 AC: 1926 AN: 4812

European-Finnish (FIN) AF: 0.348 AC: 3675 AN: 10554

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21633 AN: 67960

Other (OTH) AF: 0.316 AC: 667 AN: 2112

Alfa AF: 0.313 Hom.: 26138

Bravo AF: 0.295

Asia WGS AF: 0.471 AC: 1635 AN: 3478

EpiCase AF: 0.333

EpiControl AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.90
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.050		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: rs2272399; hg19: chr3-10975745; COSMIC: COSV54395738;