3-11028856-GCC-GCCCC

Variant names:

• chr3-11028856-G-GCC
• rs3841958
• NM_003042.4:c.1191+16_1191+17dupCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003042.4(SLC6A1):​c.1191+16_1191+17dupCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000979 in 1,571,924 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (8 hom., cov: 29)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign/Likely 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-GCC is Benign according to our data. Variant chr3-11028856-G-GCC is described in ClinVar as [Likely_benign]. Clinvar id is 1167573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00513 (776/151252) while in subpopulation AFR AF= 0.0178 (735/41202). AF 95% confidence interval is 0.0168. There are 8 homozygotes in gnomad4. There are 383 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 776 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.1191+16_1191+17dupCC		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+16_1191+17dupCC		intron_variant	Intron 11 of 15	1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 776 AN: 151134 Hom.: 8 Cov.: 29

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00338

GnomAD3 exomes AF: 0.00136 AC: 319 AN: 234778 Hom.: 1 AF XY: 0.00101 AC XY: 128 AN XY: 127144

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.000741

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000381

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000537 AC: 763 AN: 1420672 Hom.: 4 Cov.: 24 AF XY: 0.000461 AC XY: 327 AN XY: 709074

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.000765

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000431

Gnomad4 SAS exome AF: 0.0000470

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000112

Gnomad4 OTH exome AF: 0.000916

GnomAD4 genome AF: 0.00513 AC: 776 AN: 151252 Hom.: 8 Cov.: 29 AF XY: 0.00519 AC XY: 383 AN XY: 73864

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.00198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00335

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Epilepsy with myoclonic atonic seizures Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jul 26, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;