3-10885597-T-C

Position:

• chr3-10885597-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014229.3(SLC6A11):​c.891+10502T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 138,448 control chromosomes in the GnomAD database, including 35 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 0.014 (35 hom., cov: 23)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0141 (1947/138448) while in subpopulation NFE AF= 0.0161 (1013/62788). AF 95% confidence interval is 0.0153. There are 35 homozygotes in gnomad4. There are 1043 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.891+10502T>C		intron_variant		ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1	c.369+10502T>C		intron_variant			XP_047304720.1
SLC6A11	XM_011534033.3	c.891+10502T>C		intron_variant			XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.891+10502T>C		intron_variant		1	NM_014229.3	ENSP00000254488.2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 1944 AN: 138430 Hom.: 35 Cov.: 23

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.00215

Gnomad EAS AF: 0.00556

Gnomad SAS AF: 0.00699

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0138

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0140

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

GnomAD4 genome AF: 0.0141 AC: 1947 AN: 138448 Hom.: 35 Cov.: 23 AF XY: 0.0156 AC XY: 1043 AN XY: 66780

Gnomad4 AFR AF: 0.00860

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00215

Gnomad4 EAS AF: 0.00557

Gnomad4 SAS AF: 0.00752

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0139

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.75

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: rs901026; hg19: chr3-10927282;