rs3774089

Variant names:

• chr3-10914386-C-T
• rs3774089
• NM_014229.3:c.995+2193C>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.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
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 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.995+2193C>T		intron	N/A	NP_055044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.995+2193C>T		intron	N/A	ENSP00000254488.2
	SLC6A11	ENST00000861594.1		c.719+2193C>T		intron	N/A	ENSP00000531653.1
	ENSG00000286962	ENST00000656787.1		n.1337G>A		non_coding_transcript_exon	Exon 4 of 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

African (AFR) AF: 0.0494 AC: 2050 AN: 41506

American (AMR) AF: 0.291 AC: 4453 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3470

East Asian (EAS) AF: 0.149 AC: 769 AN: 5172

South Asian (SAS) AF: 0.119 AC: 573 AN: 4812

European-Finnish (FIN) AF: 0.154 AC: 1627 AN: 10578

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6949 AN: 67996

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.110 Hom.: 366

Bravo AF: 0.121

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.044
DANN	Benign	0.71
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3774089; hg19: chr3-10956071;