3-11017242-G-C

Variant names:

• chr3-11017242-G-C
• rs1264567694
• NM_003042.4:c.31G>C

Variant summary

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

The NM_003042.4(SLC6A1):​c.31G>C​(p.Gly11Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC6A1 NM_003042.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.40
• 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 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.31G>C	p.Gly11Arg	missense	Exon 3 of 16	NP_003033.3
	SLC6A1	NM_001348250.2		c.31G>C	p.Gly11Arg	missense	Exon 3 of 16	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-140G>C		5_prime_UTR	Exon 3 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.31G>C	p.Gly11Arg	missense	Exon 3 of 16	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.103G>C	p.Gly35Arg	missense	Exon 1 of 14	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.31G>C	p.Gly11Arg	missense	Exon 1 of 14	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.97	L
PhyloP100		9.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.46
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.22		Gain of MoRF binding (P = 0.005)
MVP		0.83
MPC		2.1
ClinPred		0.97	D
GERP RS		4.4
PromoterAI		0.011	Neutral
Varity_R		0.19
gMVP		0.87
Mutation Taster		=199/101	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1264567694; hg19: chr3-11058928;