3-11017248-A-T

Variant names:

• chr3-11017248-A-T
• rs1553687808
• NM_003042.4:c.37A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003042.4(SLC6A1):​c.37A>T​(p.Ile13Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I13T) has been classified as 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: 5.66
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26386455).

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.37A>T	p.Ile13Phe	missense	Exon 3 of 16	NP_003033.3
	SLC6A1	NM_001348250.2		c.37A>T	p.Ile13Phe	missense	Exon 3 of 16	NP_001335179.1
	SLC6A1	NM_001348251.2		c.-134A>T		5_prime_UTR	Exon 3 of 16	NP_001335180.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.37A>T	p.Ile13Phe	missense	Exon 3 of 16	ENSP00000287766.4
	SLC6A1	ENST00000698198.1		c.109A>T	p.Ile37Phe	missense	Exon 1 of 14	ENSP00000513602.1
	SLC6A1	ENST00000644803.1		c.37A>T	p.Ile13Phe	missense	Exon 1 of 14	ENSP00000494469.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	Benign	0.12
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.55	N
REVEL	Uncertain	0.37
Sift	Benign	0.099	T
Sift4G	Benign	0.10	T
Polyphen		0.66	P
Vest4		0.38
MutPred		0.16		Loss of glycosylation at T15 (P = 0.0777)
MVP		0.67
MPC		1.7
ClinPred		0.61	D
GERP RS		4.4
PromoterAI		-0.021	Neutral
Varity_R		0.13
gMVP		0.51
Mutation Taster		=77/23	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: rs1553687808; hg19: chr3-11058934;