chr3-10924903-A-G

Variant names:

• chr3-10924903-A-G
• rs4684746
• NM_014229.3:c.1121-1101A>G

Variant summary

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

The NM_014229.3(SLC6A11):​c.1121-1101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,244 control chromosomes in the GnomAD database, including 2,236 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 0.15 (2236 hom., cov: 33)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.1121-1101A>G		intron_variant	Intron 8 of 13	ENST00000254488.7	NP_055044.1
SLC6A11	XM_011534033.3	c.*959A>G		3_prime_UTR_variant	Exon 9 of 9		XP_011532335.1
SLC6A11	XM_047448764.1	c.599-1101A>G		intron_variant	Intron 6 of 11		XP_047304720.1
LOC105376950	XR_940587.3	n.1869+1954T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.1121-1101A>G		intron_variant	Intron 8 of 13	1	NM_014229.3	ENSP00000254488.2
ENSG00000286962	ENST00000656787.1	n.351-9531T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22551 AN: 152126 Hom.: 2224 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.148 AC: 22602 AN: 152244 Hom.: 2236 Cov.: 33 AF XY: 0.155 AC XY: 11562 AN XY: 74456

African (AFR) AF: 0.127 AC: 5272 AN: 41540

American (AMR) AF: 0.318 AC: 4858 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1567 AN: 5178

South Asian (SAS) AF: 0.220 AC: 1062 AN: 4828

European-Finnish (FIN) AF: 0.163 AC: 1724 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7539 AN: 68016

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.127 Hom.: 5206

Bravo AF: 0.161

Asia WGS AF: 0.274 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.020
DANN	Benign	0.46
PhyloP100		-2.5
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: rs4684746; hg19: chr3-10966588;