Genetic Variant SLC1A2:p.Pro201Pro (chr11-35306201-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004171.4(SLC1A2):c.603G>A(p.Pro201Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,613,208 control chromosomes in the GnomAD database, including 48,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3997 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44378 hom. )

Consequence

SLC1A2
NM_004171.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.26

Variant links:

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]

SLC1A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-35306201-C-T is Benign according to our data. Variant chr11-35306201-C-T is described in ClinVar as [Benign]. Clinvar id is 1165046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.603G>A	p.Pro201Pro	synonymous_variant	Exon 5 of 11	ENST00000278379.9	NP_004162.2	P43004-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9 link	c.603G>A	p.Pro201Pro	synonymous_variant	Exon 5 of 11	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33297

AN:

151812

Hom.:

3980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0918

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.233

AC:

58560

AN:

251040

Hom.:

7414

AF XY:

0.227

AC XY:

30757

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.208

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.242

AC:

353646

AN:

1461278

Hom.:

44378

Cov.:

AF XY:

0.237

AC XY:

172605

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.223

GnomAD4 genome

AF:

0.219

AC:

33343

AN:

151930

Hom.:

3997

Cov.:

AF XY:

0.221

AC XY:

16406

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.0910

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.240

Hom.:

10390

Bravo

AF:

0.217

Asia WGS

AF:

0.186

AC:

647

AN:

3476

EpiCase

AF:

0.247

EpiControl

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 41

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.7

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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