11-35260922-T-C

Variant names:

• chr11-35260922-T-C
• NM_004171.4:c.1697A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004171.4(SLC1A2):​c.1697A>G​(p.Glu566Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC1A2 NM_004171.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20594233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.1697A>G	p.Glu566Gly	missense_variant	Exon 11 of 11	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1697A>G	p.Glu566Gly	missense_variant	Exon 11 of 11	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 30, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;.;T;T;T;.;T;.;.;.;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.040	N;N;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.12
Sift	Benign	0.15	T;T;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.36	T;T;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.18	B;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.24
MutPred		0.18		Loss of solvent accessibility (P = 0.0098);.;.;.;.;.;.;.;.;.;.;.;.;
MVP		0.21
MPC		1.2
ClinPred		0.87	D
GERP RS		6.0
Varity_R		0.088
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr11-35282469;