3-10819753-G-A

Variant names:

• chr3-10819753-G-A
• NM_014229.3:c.433G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014229.3(SLC6A11):​c.433G>A​(p.Val145Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A11 NM_014229.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

Genes affected

SLC6A11 (HGNC:11044): (solute carrier family 6 member 11) The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3667395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.433G>A	p.Val145Met	missense_variant	Exon 3 of 14	ENST00000254488.7	NP_055044.1
SLC6A11	NM_001317406.3	c.433G>A	p.Val145Met	missense_variant	Exon 3 of 4		NP_001304335.1
SLC6A11	XM_011534033.3	c.433G>A	p.Val145Met	missense_variant	Exon 3 of 9		XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.433G>A	p.Val145Met	missense_variant	Exon 3 of 14	1	NM_014229.3	ENSP00000254488.2
SLC6A11	ENST00000454147.1	c.433G>A	p.Val145Met	missense_variant	Exon 3 of 4	1		ENSP00000404120.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.433G>A (p.V145M) alteration is located in exon 3 (coding exon 3) of the SLC6A11 gene. This alteration results from a G to A substitution at nucleotide position 433, causing the valine (V) at amino acid position 145 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.20	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.16	B;.
Vest4		0.42
MutPred		0.72		Gain of catalytic residue at I149 (P = 0.2659);Gain of catalytic residue at I149 (P = 0.2659);
MVP		0.73
MPC		0.73
ClinPred		0.67	D
GERP RS		4.4
Varity_R		0.13
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-10861438;