rs3774089

chr3-10914386-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014229.3(SLC6A11):c.995+2193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,132 control chromosomes in the GnomAD database, including 1,426 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 0.11 (1426 hom., cov: 32)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A11	NM_014229.3	c.995+2193C>T		intron_variant		ENST00000254488.7
SLC6A11	XM_011534033.3	c.995+2193C>T		intron_variant
SLC6A11	XM_047448764.1	c.473+2193C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A11	ENST00000254488.7	c.995+2193C>T		intron_variant		1	NM_014229.3	P1
	ENST00000656787.1	n.1337G>A		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16796 AN: 152014 Hom.: 1418 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16822 AN: 152132 Hom.: 1426 Cov.: 32 AF XY: 0.116 AC XY: 8612 AN XY: 74368

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.111

Alfa AF: 0.111 Hom.: 364

Bravo AF: 0.121

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.044
Dann	Benign	0.71

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: rs3774089; hg19: chr3-10956071;