3-11028856-GCC-GCCC

Variant names:

• chr3-11028856-G-GC
• rs3841958
• NM_003042.4:c.1191+17dupC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003042.4(SLC6A1):​c.1191+17dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,570,444 control chromosomes in the GnomAD database, including 313 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (183 hom., cov: 29)
  • Exomes 𝑓: 0.0050 (130 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92

Genes affected

SLC6A1 (HGNC:11042): (solute carrier family 6 member 1) The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 3-11028856-G-GC is Benign according to our data. Variant chr3-11028856-G-GC is described in ClinVar as [Benign]. Clinvar id is 475468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.1191+17dupC		intron_variant	Intron 11 of 15	ENST00000287766.10	NP_003033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10	c.1191+17dupC		intron_variant	Intron 11 of 15	1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4180 AN: 151116 Hom.: 183 Cov.: 29

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.00293

Gnomad FIN AF: 0.000287

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.0174

GnomAD3 exomes AF: 0.00906 AC: 2128 AN: 234778 Hom.: 48 AF XY: 0.00679 AC XY: 863 AN XY: 127144

Gnomad AFR exome AF: 0.0872

Gnomad AMR exome AF: 0.00769

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.00107

Gnomad SAS exome AF: 0.00225

Gnomad FIN exome AF: 0.000701

Gnomad NFE exome AF: 0.00353

Gnomad OTH exome AF: 0.00576

GnomAD4 exome AF: 0.00499 AC: 7082 AN: 1419210 Hom.: 130 Cov.: 24 AF XY: 0.00454 AC XY: 3215 AN XY: 708432

Gnomad4 AFR exome AF: 0.0863

Gnomad4 AMR exome AF: 0.00808

Gnomad4 ASJ exome AF: 0.000348

Gnomad4 EAS exome AF: 0.00127

Gnomad4 SAS exome AF: 0.00204

Gnomad4 FIN exome AF: 0.00314

Gnomad4 NFE exome AF: 0.00287

Gnomad4 OTH exome AF: 0.00732

GnomAD4 genome AF: 0.0277 AC: 4182 AN: 151234 Hom.: 183 Cov.: 29 AF XY: 0.0260 AC XY: 1922 AN XY: 73858

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.000578

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.00272

Gnomad4 FIN AF: 0.000287

Gnomad4 NFE AF: 0.00245

Gnomad4 OTH AF: 0.0172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Epilepsy with myoclonic atonic seizures Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 03, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs3841958; hg19: chr3-11070542;