Genetic Variant SLC1A3:c.*301T>C (chr5-36608922-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000512374.1(SLC1A3):c.*301T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,060,234 control chromosomes in the GnomAD database, including 61,489 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5909 hom., cov: 33)

Exomes 𝑓: 0.34 ( 55580 hom. )

Consequence

SLC1A3
ENST00000512374.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

episodic ataxia type 6
Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Laboratory for Molecular Medicine

SLC1A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5 link	c.181+318T>C		intron_variant	Intron 2 of 9	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.181+318T>C		intron_variant	Intron 2 of 9	1	NM_004172.5	ENSP00000265113.4		P43003-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37992

AN:

152134

Hom.:

5912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0944

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.258

GnomAD4 exome

AF:

0.344

AC:

312293

AN:

907982

Hom.:

55580

Cov.:

AF XY:

0.344

AC XY:

145237

AN XY:

422810

show subpopulations

African (AFR)

AF:

0.0660

AC:

1207

AN:

18294

American (AMR)

AF:

0.230

AC:

1149

AN:

4998

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

1720

AN:

8054

East Asian (EAS)

AF:

0.0939

AC:

858

AN:

9140

South Asian (SAS)

AF:

0.134

AC:

2770

AN:

20722

European-Finnish (FIN)

AF:

0.369

AC:

1283

AN:

3476

Middle Eastern (MID)

AF:

0.263

AC:

515

AN:

1958

European-Non Finnish (NFE)

AF:

0.362

AC:

293126

AN:

809152

Other (OTH)

AF:

0.300

AC:

9665

AN:

32188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9024

18047

27071

36094

45118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.249

AC:

37984

AN:

152252

Hom.:

5909

Cov.:

AF XY:

0.246

AC XY:

18317

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0824

AC:

3424

AN:

41558

American (AMR)

AF:

0.252

AC:

3852

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

710

AN:

3472

East Asian (EAS)

AF:

0.0946

AC:

491

AN:

5188

South Asian (SAS)

AF:

0.134

AC:

645

AN:

4828

European-Finnish (FIN)

AF:

0.351

AC:

3714

AN:

10584

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.356

AC:

24233

AN:

67996

Other (OTH)

AF:

0.254

AC:

538

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1385

2771

4156

5542

6927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.283

Hom.:

1579

Bravo

AF:

0.234

Asia WGS

AF:

0.106

AC:

368

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.6

(source)

DANN

Benign

0.62

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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5-36608922-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over