3-10912185-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_014229.3(SLC6A11):c.987C>T(p.Asn329=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0128 in 1,606,102 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (16 hom., cov: 32)
  • Exomes 𝑓: 0.013 (163 hom.)
• Consequence: SLC6A11 NM_014229.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.91

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 3-10912185-C-T is Benign according to our data. Variant chr3-10912185-C-T is described in ClinVar as [Benign]. Clinvar id is 3024722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A11	NM_014229.3	c.987C>T	p.Asn329=	synonymous_variant	7/14	ENST00000254488.7
SLC6A11	XM_047448764.1	c.465C>T	p.Asn155=	synonymous_variant	5/12
SLC6A11	XM_011534033.3	c.987C>T	p.Asn329=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A11	ENST00000254488.7	c.987C>T	p.Asn329=	synonymous_variant	7/14	1	NM_014229.3	P1

Frequencies

GnomAD3 genomes AF: 0.00978 AC: 1488 AN: 152184 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00236

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0114 AC: 2855 AN: 250970 Hom.: 22 AF XY: 0.0122 AC XY: 1653 AN XY: 135718

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00587

Gnomad ASJ exome AF: 0.0207

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0143

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0131 AC: 19042 AN: 1453800 Hom.: 163 Cov.: 28 AF XY: 0.0134 AC XY: 9688 AN XY: 723784

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00581

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.00976 AC: 1486 AN: 152302 Hom.: 16 Cov.: 32 AF XY: 0.00965 AC XY: 719 AN XY: 74478

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.0136 Hom.: 18

Bravo AF: 0.00899

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0144

EpiControl AF: 0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

SLC6A11: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs41308275; hg19: chr3-10953870; COSMIC: COSV104533123;