rs148429200

Variant names:

• chr3-11018638-C-T
• rs148429200
• NM_003042.4:c.411C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_003042.4(SLC6A1):​c.411C>T​(p.Asn137Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,613,836 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (9 hom.)
• Consequence: SLC6A1 NM_003042.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.150
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-11018638-C-T is Benign according to our data. Variant chr3-11018638-C-T is described in ClinVar as Benign. ClinVar VariationId is 475480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.15 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00125 (190/152330) while in subpopulation EAS AF = 0.0129 (67/5184). AF 95% confidence interval is 0.0104. There are 2 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 190 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.411C>T	p.Asn137Asn	synonymous	Exon 5 of 16	NP_003033.3
	SLC6A1	NM_001348250.2		c.411C>T	p.Asn137Asn	synonymous	Exon 5 of 16	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.51C>T	p.Asn17Asn	synonymous	Exon 5 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.411C>T	p.Asn137Asn	synonymous	Exon 5 of 16	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.483C>T	p.Asn161Asn	synonymous	Exon 3 of 14	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.411C>T	p.Asn137Asn	synonymous	Exon 3 of 14	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152212 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00250 AC: 629 AN: 251416 AF XY: 0.00219

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000881 AC: 1288 AN: 1461506 Hom.: 9 Cov.: 30 AF XY: 0.000827 AC XY: 601 AN XY: 727096

African (AFR) AF: 0.000239 AC: 8 AN: 33472

American (AMR) AF: 0.00944 AC: 422 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0202 AC: 800 AN: 39694

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111664

Other (OTH) AF: 0.000497 AC: 30 AN: 60378

GnomAD4 genome AF: 0.00125 AC: 190 AN: 152330 Hom.: 2 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74482

African (AFR) AF: 0.000313 AC: 13 AN: 41576

American (AMR) AF: 0.00640 AC: 98 AN: 15304

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

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.00172

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.42
CADD	Benign	7.8
DANN	Benign	0.91
PhyloP100		0.15
Mutation Taster		=291/9	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: rs148429200; hg19: chr3-11060324;