rs6343

Variant names:

• chr3-11017217-G-A
• rs6343
• NM_003042.4:c.6G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-11017217-G-A
• chr3-11017217-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003042.4(SLC6A1):​c.6G>A​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,613,632 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: SLC6A1 NM_003042.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.41
• Publications: 18 publications found

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]

SLC6A1-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 3-11017217-G-A is Benign according to our data. Variant chr3-11017217-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 542214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000388 (59/152234) while in subpopulation EAS AF = 0.00772 (40/5178). AF 95% confidence interval is 0.00583. There are 2 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 59 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003042.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	NM_003042.4	MANE Select	c.6G>A	p.Ala2Ala	synonymous	Exon 3 of 16	NP_003033.3
	SLC6A1	NM_001348250.2		c.6G>A	p.Ala2Ala	synonymous	Exon 3 of 16	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-165G>A		5_prime_UTR	Exon 3 of 16	NP_001335180.1	A0A2R8Y4I3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.6G>A	p.Ala2Ala	synonymous	Exon 3 of 16	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.78G>A	p.Ala26Ala	synonymous	Exon 1 of 14	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 14	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152116 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000802 AC: 201 AN: 250592 AF XY: 0.000722

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00992

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000242 AC: 353 AN: 1461398 Hom.: 2 Cov.: 31 AF XY: 0.000215 AC XY: 156 AN XY: 726928

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00539 AC: 214 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111776

Other (OTH) AF: 0.00157 AC: 95 AN: 60388

GnomAD4 genome AF: 0.000388 AC: 59 AN: 152234 Hom.: 2 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74422

African (AFR) AF: 0.000313 AC: 13 AN: 41546

American (AMR) AF: 0.000196 AC: 3 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000186 Hom.: 0

Bravo AF: 0.000450

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Epilepsy with myoclonic atonic seizures (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	SLC6A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.0
DANN	Benign	0.91
PhyloP100		-2.4
PromoterAI		-0.11	Neutral
Mutation Taster		=98/2	polymorphism

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: rs6343; hg19: chr3-11058903;