Variant chr5-36671072-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004172.5(SLC1A3):c.363G>T(p.Met121Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC1A3
NM_004172.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

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 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=0.19858536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A3	NM_004172.5 linkuse as main transcript	c.363G>T	p.Met121Ile	missense_variant	4/10	ENST00000265113.9	NP_004163.3
SLC1A3-AS1	XR_007058736.1 linkuse as main transcript	n.76-2361C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9 linkuse as main transcript	c.363G>T	p.Met121Ile	missense_variant	4/10	1	NM_004172.5	ENSP00000265113	P1	P43003-1
SLC1A3-AS1	ENST00000510740.1 linkuse as main transcript	n.61-2361C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251072

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 16, 2023

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0025

T;.;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

T;D;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.055

.;.;N;N

MutationTaster

Benign

0.59

D;D;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.25

.;.;N;N

REVEL

Benign

0.086

Sift

Benign

0.53

.;.;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.28

MutPred

0.61

Loss of methylation at R122 (P = 0.0538);.;Loss of methylation at R122 (P = 0.0538);Loss of methylation at R122 (P = 0.0538);

MVP

0.61

MPC

0.46

ClinPred

0.23

GERP RS

4.7

Varity_R

0.11

gMVP

0.64

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