chr5-36671022-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_004172.5(SLC1A3):​c.320-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,358 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

SLC1A3
NM_004172.5 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00004760
2

Clinical Significance

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

Conservation

PhyloP100: 1.75
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-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 5-36671022-C-T is Benign according to our data. Variant chr5-36671022-C-T is described in ClinVar as [Benign]. Clinvar id is 353311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-36671022-C-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC1A3NM_004172.5 linkuse as main transcriptc.320-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000265113.9 NP_004163.3
SLC1A3-AS1XR_007058736.1 linkuse as main transcriptn.76-2311G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC1A3ENST00000265113.9 linkuse as main transcriptc.320-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_004172.5 ENSP00000265113 P1P43003-1
SLC1A3-AS1ENST00000510740.1 linkuse as main transcriptn.61-2311G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000565
AC:
86
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00109
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000526
AC:
132
AN:
250872
Hom.:
0
AF XY:
0.000443
AC XY:
60
AN XY:
135566
show subpopulations
Gnomad AFR exome
AF:
0.000369
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:
0.0000462
Gnomad NFE exome
AF:
0.00109
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.00119
AC:
1740
AN:
1461186
Hom.:
3
Cov.:
31
AF XY:
0.00109
AC XY:
794
AN XY:
726962
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000112
Gnomad4 NFE exome
AF:
0.00152
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.000565
AC:
86
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.000430
AC XY:
32
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00109
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000901
Hom.:
0
Bravo
AF:
0.000597
EpiCase
AF:
0.000382
EpiControl
AF:
0.000771

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:5
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024SLC1A3: BP4, BS1, BS2 -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 30, 2023- -
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsDec 01, 2016- -
Episodic ataxia type 6 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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
BayesDel_noAF
Benign
-0.34
CADD
Benign
15
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000048
dbscSNV1_RF
Benign
0.014
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.

Other links and lift over

dbSNP: rs200867287; hg19: chr5-36671124; API