3-11017251-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Moderate BP6_Moderate

The NM_003042.4(SLC6A1):c.40T>C(p.Ser14Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A1 NM_003042.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.82

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SLC6A1
• BP4: Computational evidence support a benign effect (MetaRNN=0.1358141).
• BP6: Variant 3-11017251-T-C is Benign according to our data. Variant chr3-11017251-T-C is described in ClinVar as [Benign]. Clinvar id is 1014188.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4	c.40T>C	p.Ser14Pro	missense_variant	3/16	ENST00000287766.10
SLC6A1-AS1	NR_046647.1	n.105+1869A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10	c.40T>C	p.Ser14Pro	missense_variant	3/16	1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2	n.105+1869A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myoclonic-atonic epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.0012	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;.;T;T;.;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;.;N;.;N;N;.;.;.
MutationTaster	Benign	0.72	D;D
PrimateAI	Uncertain	0.58	T
Polyphen		0.0	B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;B;.;B;.;B;B;.;.;.
Vest4		0.38
MutPred		0.15		Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);Loss of glycosylation at S14 (P = 0.0476);
MVP		0.66
MPC		1.3
ClinPred		0.61	D
GERP RS		1.8
Varity_R		0.14
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1697187552; hg19: chr3-11058937;