rs752803485

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000265113.9(SLC1A3):​c.1612A>G​(p.Ser538Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S538C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SLC1A3
ENST00000265113.9 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.28
Variant links:
Genes affected
SLC1A3 (HGNC:10941): (solute carrier family 1 member 3) This gene encodes a member of a member of a high affinity glutamate transporter family. This gene functions in the termination of excitatory neurotransmission in central nervous system. Mutations are associated with episodic ataxia, Type 6. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2014]
SLC1A3-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

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ACMG classification

Classification made for transcript

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=0.11045548).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC1A3NM_004172.5 linkuse as main transcriptc.1612A>G p.Ser538Gly missense_variant 10/10 ENST00000265113.9 NP_004163.3
SLC1A3-AS1XR_007058736.1 linkuse as main transcriptn.76-17541T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC1A3ENST00000265113.9 linkuse as main transcriptc.1612A>G p.Ser538Gly missense_variant 10/101 NM_004172.5 ENSP00000265113 P1P43003-1
SLC1A3-AS1ENST00000510740.1 linkuse as main transcriptn.61-17541T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.0054
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.027
T;.;T;.
Eigen
Benign
-0.18
Eigen_PC
Benign
0.064
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.84
T;T;T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;.;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.1
.;.;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.016
.;.;D;D
Sift4G
Benign
0.31
T;T;T;T
Polyphen
0.0020
.;.;B;.
Vest4
0.15
MutPred
0.24
.;.;Loss of phosphorylation at S538 (P = 0.0106);.;
MVP
0.62
MPC
0.38
ClinPred
0.63
D
GERP RS
5.6
Varity_R
0.15
gMVP
0.38

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752803485; hg19: chr5-36686354; API