NM_014229.3:c.1475-7C>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.1475-7C>T		splice_region_variant, intron_variant	Intron 11 of 13	ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1	c.953-7C>T		splice_region_variant, intron_variant	Intron 9 of 11		XP_047304720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.1475-7C>T		splice_region_variant, intron_variant	Intron 11 of 13	1	NM_014229.3	ENSP00000254488.2
SLC6A11	ENST00000464828.1	n.94C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000286962	ENST00000656787.1	n.350+2931G>A		intron_variant	Intron 3 of 3

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

GnomAD3 exomes AF: 0.334 AC: 83781 AN: 250736 Hom.: 15122 AF XY: 0.342 AC XY: 46325 AN XY: 135562

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 SAS exome AF: 0.385

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

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.344

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

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.316

Alfa AF: 0.319 Hom.: 18519

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272399; hg19: chr3-10975745; COSMIC: COSV54395738;