3-10816310-T-G

Variant names:

• chr3-10816310-T-G
• rs1294213249
• NM_014229.3:c.45T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014229.3(SLC6A11):​c.45T>G​(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A15A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC6A11 NM_014229.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.998 with no splicing effect.

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.45T>G	p.Ala15Ala	synonymous	Exon 1 of 14	NP_055044.1	P48066-1
	SLC6A11	NM_001317406.3		c.45T>G	p.Ala15Ala	synonymous	Exon 1 of 4	NP_001304335.1	P48066-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.45T>G	p.Ala15Ala	synonymous	Exon 1 of 14	ENSP00000254488.2	P48066-1
	SLC6A11	ENST00000454147.1	TSL:1	c.45T>G	p.Ala15Ala	synonymous	Exon 1 of 4	ENSP00000404120.1	P48066-2
	SLC6A11	ENST00000861594.1		c.45T>G	p.Ala15Ala	synonymous	Exon 1 of 12	ENSP00000531653.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1256104 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 616620

African (AFR) AF: 0.00 AC: 0 AN: 24112

American (AMR) AF: 0.00 AC: 0 AN: 13840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18744

East Asian (EAS) AF: 0.00 AC: 0 AN: 27254

South Asian (SAS) AF: 0.00 AC: 0 AN: 57454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1015640

Other (OTH) AF: 0.00 AC: 0 AN: 50950

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.67
PhyloP100		-1.0
PromoterAI		0.0026	Neutral

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: rs1294213249; hg19: chr3-10857995;