rs2032892

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004172.5(SLC1A3):c.657G>C(p.Glu219Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,030 control chromosomes in the GnomAD database, including 474 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 86 hom., cov: 33)

Exomes 𝑓: 0.012 ( 388 hom. )

Consequence

SLC1A3
NM_004172.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.467

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 links:

SLC1A3-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

SLC1A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015866756).

BP6

Variant 5-36676981-G-C is Benign according to our data. Variant chr5-36676981-G-C is described in ClinVar as [Benign]. Clinvar id is 130326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-36676981-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5 link	c.657G>C	p.Glu219Asp	missense_variant	Exon 6 of 10	ENST00000265113.9	NP_004163.3	P43003-1A0A024R050Q8N169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9 link	c.657G>C	p.Glu219Asp	missense_variant	Exon 6 of 10	1	NM_004172.5	ENSP00000265113.4		P43003-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2971

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00660

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0247

AC:

6215

AN:

251238

Hom.:

265

AF XY:

0.0209

AC XY:

2841

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.0295

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.00667

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

AF:

0.0115

AC:

16880

AN:

1461768

Hom.:

388

Cov.:

AF XY:

0.0114

AC XY:

8266

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.00440

Gnomad4 NFE exome

AF:

0.00679

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0195

AC:

2975

AN:

152262

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.0706

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00660

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0247

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.0286

AC:

126

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.0205

AC:

2491

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.00742

EpiControl

AF:

0.00883

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21233784, 33126486, 32819603) -

not specified

Benign:2

May 01, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Episodic ataxia type 6

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

.;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.55

T;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.46

.;N;N

REVEL

Benign

0.037

Sift

Benign

0.27

.;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.071

MutPred

0.22

.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MPC

0.41

ClinPred

0.011

GERP RS

-0.25

Varity_R

0.053

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over