rs1553688027

Variant names:

• chr3-11017909-G-T
• rs1553688027
• NM_003042.4:c.305G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-11017909-G-T
• chr3-11017909-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_003042.4(SLC6A1):​c.305G>T​(p.Cys102Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C102C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A1 NM_003042.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• 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-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 12 uncertain in NM_003042.4
• 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.305G>T	p.Cys102Phe	missense	Exon 4 of 16	NP_003033.3
	SLC6A1	NM_001348250.2		c.305G>T	p.Cys102Phe	missense	Exon 4 of 16	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-56G>T		5_prime_UTR	Exon 4 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.305G>T	p.Cys102Phe	missense	Exon 4 of 16	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.377G>T	p.Cys126Phe	missense	Exon 2 of 14	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.305G>T	p.Cys102Phe	missense	Exon 2 of 14	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Epilepsy with myoclonic atonic seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	-0.17	N
PhyloP100		2.3
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.34
Sift	Benign	0.056	T
Sift4G	Uncertain	0.043	D
Polyphen		0.96	D
Vest4		0.70
MutPred		0.50		Gain of glycosylation at S103 (P = 0.1036)
MVP		0.44
MPC		2.2
ClinPred		0.92	D
GERP RS		4.1
Varity_R		0.37
gMVP		0.88
Mutation Taster		=66/34	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: rs1553688027; hg19: chr3-11059595; COSMIC: COSV55118959; COSMIC: COSV55118959;