NM_003042.4:c.715-259A>T

Variant names:

• chr3-11025190-A-T
• rs9822125
• NM_003042.4:c.715-259A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003042.4(SLC6A1):​c.715-259A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 401,686 control chromosomes in the GnomAD database, including 4,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2505 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1864 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.340
• Publications: 4 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 Gene-Disease associations (from GenCC):

• epilepsy with myoclonic atonic seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina, G2P
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-11025190-A-T is Benign according to our data. Variant chr3-11025190-A-T is described in ClinVar as Benign. ClinVar VariationId is 1261024.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

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.715-259A>T		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.715-259A>T		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.355-259A>T		intron	N/A	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.715-259A>T		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.787-259A>T		intron	N/A	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.715-259A>T		intron	N/A	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23821 AN: 152086 Hom.: 2503 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.113 AC: 28249 AN: 249482 Hom.: 1864 Cov.: 3 AF XY: 0.113 AC XY: 14408 AN XY: 127634

African (AFR) AF: 0.292 AC: 2148 AN: 7350

American (AMR) AF: 0.0903 AC: 800 AN: 8864

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 1253 AN: 8504

East Asian (EAS) AF: 0.126 AC: 2287 AN: 18190

South Asian (SAS) AF: 0.126 AC: 1995 AN: 15802

European-Finnish (FIN) AF: 0.0758 AC: 1300 AN: 17140

Middle Eastern (MID) AF: 0.159 AC: 200 AN: 1256

European-Non Finnish (NFE) AF: 0.104 AC: 16353 AN: 156502

Other (OTH) AF: 0.121 AC: 1913 AN: 15874

GnomAD4 genome AF: 0.157 AC: 23853 AN: 152204 Hom.: 2505 Cov.: 32 AF XY: 0.154 AC XY: 11489 AN XY: 74404

African (AFR) AF: 0.297 AC: 12346 AN: 41500

American (AMR) AF: 0.103 AC: 1578 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.101 AC: 523 AN: 5170

South Asian (SAS) AF: 0.134 AC: 649 AN: 4828

European-Finnish (FIN) AF: 0.0764 AC: 810 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6962 AN: 68016

Other (OTH) AF: 0.147 AC: 311 AN: 2116

Alfa AF: 0.0434 Hom.: 39

Bravo AF: 0.167

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.77
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs9822125; hg19: chr3-11066876;