SLC6A1 p.Arg479Arg

Variant names:

• chr3-11033646-C-C
• NM_003042.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-11033647--
• chr3-11033649-A-T
• chr3-11033649-A-C
• chr3-11033649-A-G
• chr3-11033647-C-A
• chr3-11033647-CGA-AGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003042.4(SLC6A1):​c. variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 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, Illumina, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.		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.		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.		intron	N/A	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.		intron	N/A	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-11075332;