Variant chr5-36608493-A-G 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.70A>G(p.Lys24Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 ( 0 hom. )

Consequence

SLC1A3
NM_004172.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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:

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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=0.11893132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A3	NM_004172.5 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	2/10	ENST00000265113.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A3	ENST00000265113.9 linkuse as main transcript	c.70A>G	p.Lys24Glu	missense_variant	2/10	1	NM_004172.5	P1	P43003-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727190

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.70A>G (p.K24E) alteration is located in exon 2 (coding exon 1) of the SLC1A3 gene. This alteration results from a A to G substitution at nucleotide position 70, causing the lysine (K) at amino acid position 24 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0093

T;.;T;T;T;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.84

T;D;D;T;.;T;D

M_CAP

Benign

0.0073

MetaRNN

Benign

0.12

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;.;L;.;.;.;L

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.47

.;.;N;N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.36

.;.;T;T;T;T;T

Sift4G

Benign

0.50

T;T;T;T;T;T;T

Polyphen

0.0

.;.;B;.;.;.;.

Vest4

0.40

MutPred

0.26

Loss of methylation at K24 (P = 0.0096);Loss of methylation at K24 (P = 0.0096);Loss of methylation at K24 (P = 0.0096);Loss of methylation at K24 (P = 0.0096);Loss of methylation at K24 (P = 0.0096);Loss of methylation at K24 (P = 0.0096);Loss of methylation at K24 (P = 0.0096);

MVP

0.60

MPC

0.59

ClinPred

0.63

GERP RS

5.7

Varity_R

0.13

gMVP

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over