3-10885597-T-C

Variant names:

• chr3-10885597-T-C
• rs901026
• NM_014229.3:c.891+10502T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	NM_014229.3	MANE Select	c.891+10502T>C		intron	N/A	NP_055044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.891+10502T>C		intron	N/A	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

African (AFR) AF: 0.00860 AC: 328 AN: 38120

American (AMR) AF: 0.00922 AC: 131 AN: 14210

Ashkenazi Jewish (ASJ) AF: 0.00215 AC: 7 AN: 3250

East Asian (EAS) AF: 0.00557 AC: 26 AN: 4664

South Asian (SAS) AF: 0.00752 AC: 31 AN: 4122

European-Finnish (FIN) AF: 0.0458 AC: 381 AN: 8326

Middle Eastern (MID) AF: 0.0152 AC: 4 AN: 264

European-Non Finnish (NFE) AF: 0.0161 AC: 1013 AN: 62788

Other (OTH) AF: 0.0139 AC: 26 AN: 1870

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		0.25
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: rs901026; hg19: chr3-10927282;