3-10888335-A-T

Variant names:

• chr3-10888335-A-T
• rs11715462
• NM_014229.3:c.891+13240A>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.891+13240A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,194 control chromosomes in the GnomAD database, including 2,217 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 0.14 (2217 hom., cov: 32)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.891+13240A>T		intron_variant	Intron 6 of 13	ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1	c.369+13240A>T		intron_variant	Intron 4 of 11		XP_047304720.1
SLC6A11	XM_011534033.3	c.891+13240A>T		intron_variant	Intron 6 of 8		XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.891+13240A>T		intron_variant	Intron 6 of 13	1	NM_014229.3	ENSP00000254488.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21928 AN: 152076 Hom.: 2216 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.144 AC: 21947 AN: 152194 Hom.: 2217 Cov.: 32 AF XY: 0.143 AC XY: 10678 AN XY: 74414

African (AFR) AF: 0.281 AC: 11658 AN: 41512

American (AMR) AF: 0.0802 AC: 1227 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1093 AN: 5162

South Asian (SAS) AF: 0.191 AC: 920 AN: 4824

European-Finnish (FIN) AF: 0.0626 AC: 664 AN: 10608

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5708 AN: 68010

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.113 Hom.: 168

Bravo AF: 0.153

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		0.10
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: rs11715462; hg19: chr3-10930020;